Microfabricated surface neurostimulation device and methods of making and using the same

ABSTRACT

Described herein are microelectrode array devices, and methods of fabrication and use of the same, to provide highly localized and efficient electrical stimulation of a neurological target. The device includes multiple microelectrode elements arranged along an supportive backing layer. The microelectrode elements are dimensioned and shaped so as to target individual neurons, groups of neurons, and neural tissue as may be located in an animal nervous system, such as along a region of a cortex of a human brain. Beneficially, the neurological probe can be used to facilitate location of the neurological target and remain implanted for long-term monitoring and/or stimulation.

CROSS REFERENCE TO RELATED APPLICATION

The present application claims benefit of U.S. Provisional ApplicationSer. No. 61/265,725 filed Dec. 1, 2009, the entire contents of which areincorporated by reference herein.

FIELD

The present disclosure relates generally to the field of interactingwith biological tissue through the use of electrical probes, and moreparticularly to interacting with a neurological target through the useof microelectrode probes.

BACKGROUND

Neurostimulation is a category of medical devices that are used totransfer electric charge or electrical fields to tissue and result in aphysiological change which benefits the patient, or performs aphysiological measurement. Neurostimulation is used today in thecochlea, the retina, the peripheral nerve system, the spine, the brainand other parts of the body.

In a particular application of Neuromodulation, conductive electrodesare placed in contact with certain cortical brain structures in order totreat certain neurological conditions. In the case of stimulating thecortical surface, for example, as described in US. Pat. App.2008/0045775, the stimulation may relieve the symptoms of Parkinson'sDisease, other movement disorders, or psychiatric disorders. In the caseof stimulating an associated region of the cortical surface, forexample, as described in U.S. Pat. No. 7,774,068, the stimulation cantreat the symptoms of movement disorders including restless legsyndrome. In the case of stimulating the temporal love of the cortex,for example, as described in US. Pat. App. 2007/0055320 or [Theodore, W.H., Fisher, R. S., “Brain stimulation for epilepsy”, Lancet Neurology, 3(2), pp. 111-118, (2004).], the stimulation can treat the symptoms oftemporal lobe epilepsy.

In the case where a cortical electrode array is used for recording andstimulation in long term therapy, an implantable pulse generatorsupplies the electrical signal to the electrode lead in contact with thebrain structure. Additionally, the implantable pulse generator canrecord neural activity and electromagnetically transmit informationoutside the body. All components are placed surgically.

In the case where a cortical electrode array is used for recording andstimulation as a diagnostic tool, it may be placed temporarily on thecortex, for example for a few weeks, and then removed when no longerrequired. The information can be captured using wearable, orimplantable, or semi-implantable, hardware.

In most prior art the electrode placed in contact with the cortex braintissue has been metallic, disc like, and relatively large in size (e.g.,3 mm in diameter). In many cases, the electrodes are as large as thebrain structures themselves. The large size of electrodes preventsspecific and precise stimulation and recording of small brain targetswhich may be responsible for disease. The resulting large electricfields and associated current paths stimulate other structures of thecortex, and do not concentrate on the intended target. Furthermore,these large electrodes cannot be used to identify the targets of thebrain by neural-recording because the area they cover is very large.

Additionally, in most prior art, cortical electrodes are placed on thesurface of dura mater which is an electrically insulating biomaterial.Placing electrodes on the dura mater, so called epidural electrodeplacement, prevents efficient charge transfer to and from the brainregion, rendering stimulation and recording less efficacious. Forexample, electric fields and associated current paths established by anepidural electrode will not concentrate electrical stimulation on theintended target. This prevents the effective delivery of potentiallytherapeutic or diagnostic neural stimulation. Additionally, for example,neural signals that epidural electrodes are trying to capture will bevery weak on the dural surface, and therefore signal-to-noise ratio willbe very low. This prevents the reliable recording of diagnostically ortherapeutically useful neural activity.

Current techniques that determine placement of such relatively largeelectrodes are accomplished by first performing a craniotomy that canvary in size but is usually at least 10 mm in diameter and be as largeas several centimeters. An electrode array is then placed upon thesurface of the cortex. Some surgeons may create a flap of the dura materand place the electrode array directly on the cortical surface.Recordings of neural activity can be made using the electrode array,from several electrode contacts. This process is complex, requiring ahighly skilled surgeon to place the electrode array, and usually ahighly skilled neurophysiologist to interpret the neural recording data.The large craniotomies that have to be performed put the patient at riskof infection and serious collateral injury.

Attempts have been made at developing microfabricated devicesspecifically designed to incorporate an array of microelectrodes whichcan stimulate small volumes of tissue on the cortex of the brain.Attempts have also been made to develop sub-dural penetratingmicroelectrodes for use on the cortex of the brain, for example, asdescribed in U.S. Pat. No. 5,215,088, “Three-Dimensional ElectrodeDevice” by Normann et al. Additionally, descriptions have been made in[Richard et al., “A neural interface for a cortical vision prosthesis”,Vision Research, 39, pp. 2577-2587, (1999)]. The prior devices howeverhave not been able to easily translate to clinical use even though theyhave been available for more than a decade. This may be a result of thematerials that are required to construct the device, because Silicon isa brittle material which may easily break during implantation orremoval. Additionally, the reason for the lack of success may be becausetheir functions do not provide enough additional information to thesurgical team, because they only provide one electrode per penetratingshaft.

An important requirement for a successful outcome of corticalstimulation therapy, is the accurate placement of the stimulation andrecording electrodes within the stimulation target area. Mislocation mayresult in unwanted side-effects, including sensory motor deficits.Additionally, a mislocated recording electrode will yield little or norelevant physiological data to the surgical team. Prior art proceduresapproximately localize the target by pre-surgical imaging and planning,for example through Trans-Cranial Magnetic Stimulation as described in[Komssi et al., “The effect of stimulus intensity on brain responsesevoked by transcranial magnetic stimulation”, Human Brain Mapping, 21(3), pp. 154-164, (2004)] to identify a region of therapeutic interest.The targets themselves may be only a few mm or less, and not bedetectable through standard imaging techniques alone. Thereforeexploratory surgical procedures involving acute stimulation, many timeswith the patient awake during the procedure, are necessary. Once theprecise target area is located, the acute or chronic recording andstimulation electrodes can be implanted at the precise location.

Disadvantages of the current technology include extension of operationtime by several hours, which can be an increased burden for the patient,who may be awake during such procedures, and extended cost associatedwith lengthier procedures which are a heavy financial burden onhealthcare providers. Increased risk of surgical complications frombleeding or tissue damage caused by large craniotomies or repeatedlyplaced electrode arrays are a major risk of infection for the patient.Additionally, the possibility that chronic electrode arrays are notprecisely located at identified target for any number of reasons,including further brain movement require that patients return tosurgery.

SUMMARY

For efficient stimulation of cortical brain structures, an array ofsubdural penetrating microelectrodes are required. After placement ofthe microelectrode array, the surgeon should be able to identify thearea of the brain that requires stimulation by recording from themicroelectrodes. Subsequently the surgeon should stimulate theidentified structure.

For more efficient diagnostic and therapeutic use in cortical brainstructures, subdural penetrating microelectrodes that create athree-dimensional volume of stimulation and recording functionality aredescribed.

The disclosure describes a system which places many microelectrodestructures on the cortex of the brain, and allows the surgeon to apply asignal to each microelectrode separately, in parallel, or between atleast two microelectrodes. Furthermore, using electronics to recordneural activity from the system, the surgeon can develop a localized mapof neural activity in the cortical region in which the electrode isimplanted.

In one aspect, the disclosure relates to an implantable neurologicalprobe. The neurological probe includes at least one protrusion on whichat least one microelectrode elements are disposed on the surface of theprotrusion. The microelectrode elements can perform neural stimulationor neural recording. The neurological probe preferably has severalprotrusions, and the protrusions preferably have several microelectrodeselements, or an array of microelectrode elements. Attached to theneurological probe, either on its surface, or connected through atethered ensemble of wires, is the control circuitry. The controlcircuitry is itself encapsulated in a wearable or implantable enclosure.The neurological probe includes at least one electrical connection, orelectromagnetic link, to the control circuitry. The control circuitrysends stimulation signals to the neurological probe. The controlcircuitry can also capture neurophysiological signals from theneurological probe. The control circuitry may connect telemetrically toyet another external controller, which can be used to transmit signalsto and from the neurological probe, via the attached control circuitry.

In another aspect, the disclosure relates to a process for stimulating aneurological target. The process includes implanting a neurologicalprobe at or near the target site on the cortex. The neurological probeitself comprises a supportive backing layer, at least one protrusionfrom the supportive backing layer, and at least one microelectrodeelement on each protrusion. Additionally, each of the at least onemicroelectrode elements are in electrical communication with either aproximal electrical contact, or in electrical communication with thecontrol circuitry. The proximal electrical contact may be connected to aneurological stimulation source supplying an electrical signal.Alternatively, the control circuitry may be supplying the electricalsignal to the microelectrode element. The supplied signal is applied toone or more of the microelectrode elements. The one or more energizedmicroelectrode elements produce an electric field adapted to stimulatethe neurological target site.

In yet another aspect, the disclosure relates to a process for recordingfrom a neurological target. The process includes implanting aneurological probe at or near the target site on the cortex. Theneurological probe itself comprises a supportive backing layer, at leastone protrusion from the supportive backing layer, and at least onemicroelectrode element on each protrusion. Additionally, each of the atleast one microelectrode elements are in electrical communication witheither a proximal electrical contact, or in electrical communicationwith the control circuitry. The proximal electrical contact may beconnected to a neurological recording source, such as an amplifieracquisition system. Alternatively, the control circuitry may beacquiring and recording the neurophysiological signal from themicroelectrode element. The acquired signal may be transmitted from thecontrol circuitry to the external controller. The one or more recordedmicroelectrode elements produce data on the electrophysiologicalactivity of the neurological target site.

In another aspect, the disclosure relates to an implantable devicecomprising several neurological probes, where each neurological probesincludes a supportive backing layer, at least one protrusion extendingaway from a surface of the supportive backing layer and at least onemicroelectrode element arranged along the at least one protrusion. Theneurological probes may be connected to each other by tethered wires.Alternatively the neurological probes may be in telemetriccommunication.

In another aspect, the disclosure relates to an implantable neurologicalprobe which includes a supportive backing layer, at least one protrusionextending away from a surface of the supportive backing layer and atleast one microelectrode element arranged along the at least oneprotrusion.

In another aspect, the disclosure relates to a process for stimulating aneurological target by implanting a neurological probe within a vicinityof a cortical target site. The neurological probe includes a supportivebacking layer, at least one protrusion extending away from a surface ofthe supportive backing layer. At least one microelectrode element isarranged along the at least one protrusion. The at least onemicroelectrode element is energized by a supplied electrical signal,wherein the at least one microelectrode element produces an electricfield adapted to stimulate the neurological target site.

In another aspect, the disclosure relates to an implantable neurologicalsurface probe includes a supportive backing layer and a number ofprotrusions. Each protrusion is attached at one end to the supportivebacking layer and extends away from a surface of the supportive backinglayer. The probe also includes a microelectrode film disposed along atleast a portion of the supportive backing layer. A number ofmicroelectrode elements are disposed on the microelectrode film andarranged along each of the number of protrusions. Each microelectrodeelement is disposed at a respective depth measured from the surface ofthe supportive backing layer.

In yet another aspect, the disclosure relates to a process of making animplantable neurological surface probe includes shaping a supportivebacking layer and defining within the supportive backing layer a numberof rigid backing members. Each of the rigid backing members has a tip atone end and is attached to the supportive backing layer at another end.Each rigid backing member is bent at its attached end away from asurface of the supportive backing layer, forming a number ofprotrusions. A number of microelectrode elements are formed on amicroelectrode film, and the microelectrode film is fastened along atleast a portion of the surface the supportive backing layer. The film isfastened such that respective subsets of the plurality of microelectrodeelements are arranged along each of the plurality of protrusions. Whenso arranged, each microelectrode element of each respective subset isdisposed at a respective depth measured from the surface of thesupportive backing layer.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of thedisclosure will be apparent from the following more particulardescription of preferred embodiments of the disclosure, as illustratedin the accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingthe principles of the disclosure.

FIG. 1 is a perspective view of one embodiment of a corticalneuromodulation device.

FIG. 2 is a perspective view of a portion of a human anatomyillustrating an exemplary cortical neuromodulation device implantedtherein.

FIG. 3 is a cross-sectional view of a portion of a human cortex anatomyillustrating an exemplary neurological surface probe positioned on thesurface of the brain.

FIG. 4 is a schematic view of the components that are incorporated inthe cortical neuromodulation device.

FIG. 5A is a top view of the cortical neuromodulation device in FIG. 1.

FIG. 5B is detailed view of the control module of the corticalneuromodulation device in FIG. 1.

FIG. 6A is a detailed view of the neurological surface probe in FIG. 1.

FIG. 6B is an additional detailed view of the neurological surface probein FIG. 1.

FIG. 6C is a perspective view of the neurological surface probe in FIG.1 where currents have been applied to the microelectrodes.

FIG. 6D is an additional perspective view of the neurological surfaceprobe in FIG. 1 where currents have been applied to the microelectrodesdemonstrating electric field isosurfaces.

FIG. 7A is a front view of the neurological surface probe in FIG. 1.

FIG. 7B is a side view of the neurological surface probe in FIG. 1.

FIG. 7C is a top view of the neurological surface probe in FIG. 1.

FIG. 8A is a perspective view of a protrusion from the supportivebacking layer of the neurological surface probe in FIG. 1.

FIG. 8B is an additional perspective view of a protrusion from thesupportive backing layer of the neurological surface probe in FIG. 1.

FIG. 9 is a top view of the supportive backing layer and microelectrodefilm that are incorporated in a neurological surface probe before theyhave been attached.

FIG. 10 is a top view of the supportive backing layer and microelectrodefilm that are incorporated in a neurological surface probe after theyhave been bonded.

FIG. 11A is a perspective view of a cross section of human anatomydemonstrating the placement of the cortical neuromodulation device ofFIG. 1.

FIG. 11B is an additional perspective view of a cross section of humananatomy demonstrating the placement of the cortical neuromodulationdevice of FIG. 1.

FIG. 11C is an additional planar view of a cross section of humananatomy demonstrating the placement of the cortical neuromodulationdevice of FIG. 1.

FIG. 12 is a perspective view of an alternative embodiment of a corticalneuromodulation device.

FIG. 13 is an additional perspective view of the alternative embodimentof the cortical neuromodulation device in FIG. 12.

FIG. 14 is a top planar view of the alternative embodiment of thecortical neuromodulation device in FIG. 12.

FIG. 15 is a perspective view of a cross section of human anatomydemonstrating the placement of the cortical neuromodulation device ofFIG. 12.

FIG. 16 is an additional perspective view of a cross section of humananatomy demonstrating the placement of the cortical neuromodulationdevice of FIG. 12.

FIG. 17A is a perspective view of an exemplary embodiment of a circularcortical neuromodulation device.

FIG. 17B is an additional perspective view of an exemplary embodiment ofa circular cortical neuromodulation device shown in FIG. 17A.

FIG. 17C is a perspective view of a circular cortical neuromodulationdevice where currents have been applied to the microelectrodes.

FIG. 17D is an additional perspective view of a circular corticalneuromodulation device where currents have been applied to themicroelectrodes demonstrating electric field isosurfaces.

FIG. 18A is a planar view of a component required to implement thecircular cortical neuromodulation device shown in FIG. 17A.

FIG. 18B is a planar view of the microelectrode array film required toimplement the circular cortical neuromodulation device shown in FIG.17A.

FIG. 18C is a planar view of a component required to implement analternative embodiment of the circular cortical neuromodulation deviceshown in FIG. 17A.

FIG. 18D is a planar view of the microelectrode array film required toimplement an alternative embodiment of the circular corticalneuromodulation device shown in FIG. 17A.

FIG. 18E is a perspective view of the alternative embodiment of thecircular cortical neuromodulation device components shown in FIG. 18Cand FIG. 18D.

FIG. 19A is a planar view of a cross section of human brain anatomydemonstrating the placement of the circular cortical neuromodulationdevice of FIG. 17A.

FIG. 19B is an additional planar view of human brain anatomydemonstrating the placement of the circular cortical neuromodulationdevice of FIG. 17A.

FIG. 20A is a planar view of human brain anatomy demonstrating theplacement of a multiplicity of circular cortical neuromodulation devicesof FIG. 17A.

FIG. 20B is a detailed perspective view of human brain anatomydemonstrating the placement of a multiplicity of circular corticalneuromodulation devices of FIG. 17A.

FIG. 21A is a perspective view of an additional embodiment of a circularcortical neuromodulation device.

FIG. 21B is an additional perspective view of the circular corticalneuromodulation device shown in FIG. 21A.

FIG. 21C is planar view of the circular cortical neuromodulation deviceshown in FIG. 21A.

FIG. 22 is a perspective view of human brain anatomy demonstrating theplacement of a circular cortical neuromodulation device of FIG. 21A.

FIG. 23 is a detailed perspective view of human brain anatomydemonstrating the placement of a cortical neuromodulation device of FIG.21A.

FIG. 24 is a detailed perspective view of human brain anatomydemonstrating a multiplicity of implanted circular corticalneuromodulation devices of FIG. 21A

FIG. 25A through FIG. 25M illustrate cross sections of an exemplarymicroelectrode device at various different stages of constructionaccording to an exemplary fabrication procedure.

FIG. 26 is a micrograph of an embodiment of a microelectrode.

FIG. 27 is a planar view of a construction element of an embodiment of amicroelectrode tip.

FIG. 28 is a schematic view of a portion of the construction elementillustrated in FIG. 27.

FIG. 29 is an exploded schematic view of a construction element of anembodiment of a microelectrode tip.

FIG. 30 is a schematic view of another portion of the constructionelement.

FIG. 31 is a perspective view of a distal portion of a microelectrodetip.

FIG. 32 is a cross sectional view of the distal portion of themicroelectrode tip illustrated in FIG. 31.

FIG. 33A is a planar view of a construction element of a microelectrodearray assembly.

FIG. 33B is a perspective view of a construction element of amicroelectrode array assembly.

FIG. 33C is a perspective view of a construction element of amicroelectrode array assembly shown in FIG. 33B after the rigid backingmembers have been assembled into position

FIG. 34A is a planar view of a construction element of a microelectrodearray assembly.

FIG. 34B is a planar view of a construction element of a microelectrodearray assembly.

FIG. 34C is a more detailed planar view of a construction element of amicroelectrode array assembly.

FIG. 34D is a more detailed planar view of an alternative embodiment ofa construction element of a microelectrode array assembly.

FIG. 35A is a perspective view of a microelectrode array assembly.

FIG. 35B is a more detailed perspective view of a microelectrode arraytip.

FIG. 35C is a perspective view of an alternative embodiment ofmicroelectrode array assembly.

FIG. 35D is a more detailed perspective view of an alternativeembodiment of a microelectrode array tip.

FIG. 35E is a perspective view of the microelectrode array assemblyshown in FIG. 35A.

FIG. 36A is a view of a portion of a human anatomy illustrating anexemplary microelectrode structure positioned at a neurological target.

FIG. 36B is an additional view of a portion of a human anatomyillustrating an exemplary microelectrode structure positioned at aneurological target.

FIG. 36C is a more detailed view of a portion of a human anatomyillustrating an exemplary microelectrode structure positioned at aneurological target.

FIG. 37 is a functional block diagram of an exemplary embodiment of aneurological microelectrode system configured in stimulation mode.

FIG. 38 is a functional block diagram of an exemplary embodiment of aneurological microelectrode system configured in routing mode.

FIG. 39 is a functional block diagram of another embodiment of aneurological microelectrode system.

FIG. 40 is an electronic circuit schematic diagram for an exemplary onboard microelectronic circuit.

FIG. 41A is a schematic view of an embodiment of a neurological targetstimulator.

FIG. 41B is a schematic view of an embodiment of a neurological targetstimulator system.

FIG. 42A through FIG. 42D are a schematic views of various alternativeembodiments of a microelectrode array.

FIG. 43A through FIG. 43J are schematic views of various alternativeembodiments of a cortical depth microelectrode array.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Described herein are microelectrode array devices, and methods offabrication and use of the same, to provide highly localized andefficient electrical stimulation of a neurological target, such asindividual neurons, groups of neurons, and neural tissue as may belocated in an animal nervous system, such as the human cortex. Inindications where it is difficult to determine the final positioning ofthe microelectrode for diagnostic or therapeutic use, it is beneficialto safely implant many electrodes in the target region, and then proceedto determine the best electrode by applying an electrical signal forneural stimulation or performing neural recording. A higher number ofmicroelectrodes, and more specifically a higher number of microelectrodein a three-dimensional volume, will increase the probability that thebest therapeutic or diagnostic region is in contact with amicroelectrode.

The stimulation can be highly localized, because the microelectrodeelements can be as small as only 2 μm or large as 2 mm in either ofdiameter or width. The relative spacing between such microelectrodeelements can also be as small as only 2 μm or as large as 2 mm. Although2 μm are indicated as lower limits to either dimension or spacing, otherembodiments are possible having dimensions and/or inter-element spacingof less than 2 μm, as may be practically limited by fabricationtechniques. Generally, microelectrodes in the form of a disc of about100 μm in diameter, with about a 500 μm spacing are particularlyefficient in recording from neural tissue in the cortex. Additionally,microelectrodes in the form of a disc of about 300 μm diameter, withabout a 500 μm spacing are particularly efficient in stimulating neuraltissue in the cortex. An array of such microelectrode elements mayconsist of one or more such elements (e.g., four elements), eachdisposed at a respective position along a support structure. There isadditionally an array of support structures that can be all be arrangedto protrude from a supportive backing. In this manner, a multiplicity ofmicroelectrode elements can be arranged in three-dimensional space. Thisis in contrast to currently available epidural recording and stimulationleads, such as the RNS® System from NeuroPace Corp. (Mountain View,Calif.) which may be marketed in the future. Additionally, grid andstrip electrodes are marketed for transient use from Integra Corp. (NewJersey, N.J.). Such commercially available devices include relativelylarge, disc electrodes measuring about 3 mm in diameter, with largespacing between each electrode (i.e., 5 mm) and only generate a twodimensional area of targeting in the epidural region of the cortex. Itwould be beneficial to have a system that can provide athree-dimensional volume of influence in the subdural area of thecortex, in order to perform better neural recording and provide moreefficacious neural stimulation.

Smaller microelectrode elements can be used to provide neurologicalstimulation that is highly localized and efficient because an array ofsuch microelectrodes can also be used to identify the stimulation regionof interest. For example, one or more microelectrode elements of such anarray of microelectrode elements can be used to detect and, in someinstances, record neuronal activity in the vicinity of thedetecting/recording microelectrode elements. Such refinement offered bythe relatively small size and/or spacing of the microelectrode elementscan be used to obtain a highly localized map of neuronal activity in thethree-dimensional volume surrounding the implant. A suitably dimensionedmicroelectrode array, and a suitably dimensioned supportive backinglayer, can have multiple microelectrode elements positioned in a generalvicinity of a neurological target. The array can therefore be used tolocate a precise neurological target without further repositioning, byidentifying those one or more microelectrode elements located in a veryspecific region of the neurological target. The microelectrode array canbe programmed to stimulate in a very specific region, for example, usingonly a certain number of the microelectrode elements to activelystimulate the surrounding neurons and/or neuronal tissue, while otherelectrode elements of the array remain inactive.

In some embodiments, a three-dimensionally arranged neurological surfaceprobe includes such a multiplicity of microelectrode arrays havingelements with relatively small size and/or spacing that can be used toobtain a highly localized map of neuronal activity in the regionsurrounding the implant. For example, such a device configured with aseveral linear arrays of microelectrodes can be surgically placed ontothe surface of the patient's brain (i.e., the cortex). Preferably, theelements of the microelectrode arrays span a region including theneurological target. Neurological activity can then be independentlydetected by one or more of the microelectrode elements. The detectedactivity may be captured in a recorder or display device, allowing aclinician to identify which one or more of the microelectrode elementsis positioned closest to the intended target. Beneficially, location ofthe target can be determined without any repositioning of the elongateddevice, thereby simplifying the medical procedure and reducing patientrisk.

In some embodiments, the device is used only transiently, or acutely,being removed after the target has been located, being replaced with achronic probe, positioned at the determined target location.Alternatively or in addition, the device itself can be left in place asa chronic device, the same microelectrodes, or different ones, beingused to record and/or stimulate the neurological target over an extendedperiod.

One embodiment of a neurological surface probe illustrated in FIG. 1includes a neurological device assembly referred to as a corticalneuromodulation device 100. The cortical neuromodulation device 100includes a neurological surface probe 101 and a control module 150. Theneurological surface probe 101 is located on the distal portion of thecortical neuromodulation device 100, and the control module 150 islocated on the proximal portion of the cortical neuromodulation device100. The neurological surface probe 101 is comprised of two components,the supportive backing layer 120 and the microelectrode array film 110.In this embodiment nine protrusions from the neurological surface probeare referred to as cortical depth probes 130. On the surface of eachcortical depth probe is a linear array of microelectrode elements 140.The neurological surface probe 101 is attached to the control circuitry150 via a ribbon cable tether 180. The control module 150 is comprisedof a lower housing 151 and an upper housing 152. The lower housing 151may also incorporate at least one fixation structure 156 which is usedto fix the control module 150 the skull. In the current embodiment threefixation structures 156 a, 156 b, 156 c are provided which incorporatethrough holes for cranial fixation screws. Inside the control module 150is the control circuitry 160 which is comprised of an electroniccircuit. In the current embodiment the control circuitry 160 iscomprised of three individual and interconnected control circuits 160 a,160 b, 160 c. Additionally, inside the control module 150 a loop antenna165 is connected to the control circuitry 160 and is used tocommunicated information to and from the control module 150extra-corporeally. In the exemplary embodiment, each of themicroelectrode elements 140 is in electrical communication with thecontrol circuitry 160 via a respective electrical conductor disposed inthe microelectrode array film 110 and the ribbon cable tether 180. Inuse, stimulation signals are directed from the control circuitry 160 tothe microelectrode elements 140. Additionally, in use, recordedneurophysiological signals are directed from the microelectrode elements140 to the control circuitry 160. Furthermore, in use, the controlcircuitry 160 is programmed to function by an external control system(not shown) through the loop antenna 165. The control circuitry 160 canalso transmit information about the recorded neurophysiological signalsto the external control system (not shown) through the loop antenna 165.

The size and shape of the control module 150 can vary, but is generallyintended to be implanted on the surface of the skull. The size and shapeof the neurological surface probe 101 can vary, but is generallyintended to be implanted on the surface of the cortex. The size andshape of the cortical depth probes 130 can vary, but are generallyintended to penetrate the layers of the cortex. Finally, the size,shape, and quantity of the microelectrode elements 140 can vary, but aregenerally intended to record from the cortical layers and stimulate thecortical layers. The neurological surface probe 101 is shown as asquare. Alternatively, in some embodiments the neurological surfaceprobe 101 is circular. Alternatively, in some embodiments theneurological surface probe 101 is rectangular. The neurological surfaceprobe 101 is shown with all cortical depth probes 130 descended andprotruding from its surface. Alternatively, in some embodiments not allof the cortical depth probes 130 are descended. Alternatively, in someembodiments the cortical depth probes 130 are descended only at the timeof surgery, once the surgeon has decided which cortical depth probes 130are necessary.

The cortical neuromodulation device 100 is preferably sized and shapedfor its intended neurological application. The cortical neuromodulationdevice 100 is not limited for use in the animal or human cortex. Forexample, the cortical neuromodulation device 100 may be at leastpartially placed within the central nervous system. Alternatively or inaddition, the cortical neuromodulation device 100 may be used withinother parts of the body, such as the retina, the cochlea, the epiduralspace of the spine, the spine, and other locations within the peripheralnervous system. Thus the diameter and length of the corticalneuromodulation device 100 may vary depending on the particularanatomical target. Additionally, the configuration of the neurologicalsurface probe 101 and the cortical depth probes 130 are sized and shapedfor an intended neurological target. The number, shape, orientation,size, and spacing of the microelectrode elements 140 can be defined inresponse to the intended neurological target.

In at least some embodiments one or more of the microelectrode elements140 are sized and or spaced to record from and/or stimulate a singleneuron, or group of neurons. The cortical neuromodulation device 100 canbe used to detect and/or record neuronal activity at the neurologicaltarget. Neuronal activity naturally occurring within the neurologicaltarget gives rise to local electromagnetic fields that can be detectedby one or more of the microelectrode elements 140 of the cortical depthprobe 130. For example, electric fields produced by neurons willpolarize one or more of the microelectrode elements 140. Suchpolarization gives rise to an electrical potential with respect to areference, such as electrical ground, or another one of themicroelectrode elements 140. Such electric activity can be furtherconducted to the control circuitry 160 through the internal electricalconductors in the ribbon cable tether 180. The control circuitry 160 canthen electromagnetically transmit captured data of the detectedelectrical activity for further processing by an external controller(not shown). For example, the captured data can be displayed on acomputer.

Alternatively or in addition, one or more of the microelectrode elements140 can be used to electrically stimulate the neurological target. Forexample, one or more electrical signals generated by the control circuit160 can be applied to one or more of the microelectrode elements 140.These electrical signals can be conducted through the internalelectrical conductors in the ribbon cable tether 180 to one or more ofthe microelectrode elements 140 of the microelectrode array film 110.Depending on the amplitude and polarity of the electrical signals, anelectrical field will be induced by the polarized microelectrodeelements 140. Electrical fields induced by such polarization caninteract with one or more neurons at the neurological target.

In some embodiments, at least a portion of the control module 150 can beextracorporeal. Alternatively or in addition, the stimulation source canbe implanted in the body. Any implanted elements of the stimulationsource are preferably fabricated and/or contained with a hermeticallysealed, bio-compatible envelope. Such bio-compatible packaging of signalsources is well known, for example, in the area of artificialpacemakers. The stimulation source, when provided, may be a controllablesignal generator producing a desired signal according to a prescribedinput. For example, the signal generator may receive an input indicativeof a desired output stimulation signal frequency. Such outputstimulation signals can have a variety of wave forms, such as pulses,charged balanced pulses, sinusoidal, square wave, triangle wave, andcombinations of such basic wave forms.

In some embodiments, the stimulation source includes a pulse generatorfor applying signals to the microelectrode elements 140. The signalsfrom the pulse generator can be connected directly to themicroelectrodes, or they can be preprocessed using electronics. In someembodiments, such preprocessing electronics are embedded within theimplantable device. The preprocessing electronics can filter certainparts of an original signal, such as a cardiac pacemaker signal, inorder to select preferred frequency components of the original signalthat are at or near a peak resistance frequency of the microelectrodes.For embodiments in which there are more microelectrodes than signals,electronics can route the stimulation signals to preferred one or moreof the microelectrodes.

Microfabricated Components

A microfabrication procedure can be used to implement electricallyconductive traces within an insulative substrate to form any of themicroelectrode array devices described herein, whether the array devicesare rigid or flexible. The microfabricated components include portionsof the microelectrode array assembly. The microelectrode array can beimplemented in a polymeric material such as polyimide or parylene andincludes thin film or plated layers of a metal or metal oxide with highcharge transfer capability such as platinum, platinum-iridium, iridium,iridium oxide or titanium. In some embodiments, other metals, metalalloys, carbon based conductive materials, and electrically conductivematerials, such as doped semiconductors, conductive polymers, andconductive ceramics may be used. In some embodiments, the polymeric andmetallic layers are deposited sequentially and formed using establishedprinciples of microfabrication such as spin coating, DC/RF sputtering,photolithography, plasma etching, and etching with a mask consisting ofa secondary or sacrificial material such as silicon dioxide orphotosensitive resist.

The metallic layer is formed to create one or more of the microelectrodearray elements and electrically conductive traces that connect the arrayelements to one or more of the electronics. In some embodiments, themicroelectrode array includes multiple layers. For example, thepolymeric layers serve to isolate the traces from each other, while alsoproviding the structure of the implant's stimulating/recording tip.There are several fabrication methods which can be described to buildsuch a microfabricated component.

The insulative substrate can be a polymer, such as a polyimide orparylene but can also be polyurethane or polysiloxane (silicone), or anyother suitable insulator. For substantially non-flexible, or rigidembodiments, a rigid or semi-rigid substrate can be included. In someembodiments, the microelectrode array film 110 is formed on at least onesurface of a rigid substrate, such as a planar ceramic member.Alternatively or in addition, one or more rigid or semi-rigid supportingmembers can be attached during fabrication to provide a desired amountof rigidity. Generally, the microfabricated component can be fabricated,for example, using a series of additive and subtractive processes thatproduce a stack of materials.

The supportive backing layer 120 provide a rigid or semi-rigid supportto the microelectrode array film 110. It can be implemented in a varietyof biocompatible materials, such as stainless steel, polyimide, orpolyetheretherketone (PEEK). The supportive backing layer can bestructured using laser micromachining processes, stamping, forming, orinjection molding methods. In the case that the supportive backing layer120 is of a conductive material, it may also form electrical ground forthe stimulation or recording of signals. The supportive backing layer120 is generally a relatively thin structure, between 50 um to 2 mm. Thesupportive backing layer 120 should be amenable to being slightlydeformed in order to create protrusions from its surface, such as thecase with the cortical depth probes 130 that it supports.

Mechanical components of the cortical neuromodulation device 100 includethe supportive backing layer 120, and the control module 150. In someembodiments, the control module 150 may be implemented directly on thesurface of the neurological surface probe 101. In the current embodimentit is implemented separately, but is attached via a ribbon cable tether180. Alternatively, in some embodiments there is no control module 150,and the electrical conductors embedded in the microelectrode array film110 and the ribbon cable tether 180 are connected directly to anexternal system through the patient's skin.

The electrical components can be discrete or microelectronic parts.Their purpose is to filter, route, generate, or process signals to andfrom the microelectrode elements 140. They can be attached to thecontrol circuit 160 during production, or bonded afterwards.Alternatively, the can be bonded directly to the microelectrode arrayfilm 140. The loop antenna 165 is intended to transmit and receivesignals in the control circuitry. All electrical components aregenerally contained within the control module 150.

The cortical neuromodulation device 100 can be implanted near aneurological target, such as a target brain structure, using commonneurosurgical techniques such as stereotaxy or endoscopy. The corticalneuromodulation device 100 can be inserted without support, or attachedto a stereotactic tool. Generally, the neurological surface probe 101will be implanted in one surgical step, while the control module 150will be implanted in an additional surgical step. The neurologicalsurface probe 101 is intended to be implanted subdurally, through acraniotomy. The cortical depth probes 130 are intended to be rigidenough to penetrate the dura mater. However, the surgeon may also decideto create a flap of the dura mater during surgery, and thereby theneurological surface probe 101 will be implanted subdurally. The controlmodule 150 is intended to be implanted on the surface of the skull andfixated to the bone matter using screws.

A clinician can direct the captured neurological recordings from themicroelectrode elements 140 to a display unit. The information can betransmitted wirelessly using the loop antenna 165. Alternatively, in thecase that the cortical neuromodulation device 100 does not include acontrol module 150, the information can be transmitted directly throughthe ribbon cable tether 180 to an external controller (not shown). Therecorded data allows a clinician to identify certain regions of thebrain according to their electrical activity. In some embodiments, suchrecording information can be processed automatically. The processing, orpart of the processing, can be performed by the control circuit 160before transmitting it wirelessly to an external controller.Alternatively, in the case that the cortical neuromodulation device 100does not include a control module 150, the processing is performedentirely by the external controller (not shown). The microelectrodeelements 140 used to record from the brain can be the samemicroelectrode elements 140 as those used to stimulate tissue. Therecording electrodes can also be separate from those used to stimulatethe brain. This situation might be preferred because electrodes destinedfor recording may be different in size and design than those forstimulation.

A perspective view of the portion of a human anatomy is illustrated inFIG. 2, showing implantation of an exemplary cortical neuromodulationdevice 100 positioned for interaction with a neurological target 200located on the cortex of the human brain 220. The distal portion of thecortical neuromodulation device 100 is the neurological surface probe101 and is positioned at the neurological target 200, in this instancelocated within the human brain 220. In this embodiment the proximal endof the cortical neuromodulation device 100, i.e., the control module150, is attached to the distal end through a ribbon cable or wirebundle. This minimizes the size of the device implanted directly in thebrain. In some embodiments the control module 150 is small enough to beintegrated directly with the neurological surface probe 101.Alternatively, the control module 150 can be implanted at a remoteportion of the subject body 210, such as the upper chest. One or morecortical neuromodulation devices 100 can be implanted in differentcortical brain regions.

Referring now to FIG. 3, a cross-sectional view of a portion of a humanbrain anatomy 200 is shown, illustrating an exemplary neurologicalsurface probe 101 positioned at a neurological target 200 (e.g., thecortex as shown). The neurological surface probe 101 includes an arrayof nine cortical depth probes 130. On the surface of each cortical depthprobe 130 is an array of microelectrode elements 140 distributedlinearly. In this exemplary embodiment, there are four microelectrodeelements 140 on each cortical depth probe 130. Preferably, the corticaldepth probe 130 and microelectrode elements 140 are shaped and sized toallow one or more of the microelectrode elements 140 to be positioned ina clinically relevant cortical layer 201 a 201 b or 201 c (collectively201). Additionally, in some embodiments, it may be advantageous for thedevice to fit between two sulci 205, the natural folds of the cortex.This is important in terms of safety for the patient.

As illustrated, one or more of the microelectrode elements 140 (on thecortical depth electrodes 130 protruding from the neurological surfaceprobe 101) are positioned in direct contact with the neurological target200. The planar component of the neurological surface probe 101 remainson the surface of the brain 221. In some surgical procedures the planarcomponent of the neurological surface probe 101 remains above the duramater, while the cortical depth probes 130 are below the dura mater. Inalternative surgical procedures the planar component of the neurologicalsurface probe 101 is below the dura mater, requiring the formation of aflap of the dura mater during the surgery. Regardless of the formationof a dural flap during the surgery, in most procedures, the corticaldepth probes 130 are subdural, and the microelectrode elements 140 areintended to be in contact with several cortical layers 201.

In some embodiments, selectable microelectrode elements 140 can beactivated to record from the neurological target 200. Additionally,recordings of neurological activity from microelectrode elements 140 canbe used to identify the location or position of the microelectrodeelement 140. For example, a microelectrode element 140 that is recordingfrom cortical layer 201 a will have a different signal than amicroelement 140 that is recording from cortical layer 201 b. As anadditional example, a microelectrode element 140 that is recording fromcortical layer 201 b will have a different signal than a microelement140 that is recording from cortical layer 201 c. In this manner, thephysician can determine the positioning of the microelectrode elements140, and the neurological surface probe 101 in the neurological target200.

In some embodiments, the microelectrode elements 140 that are used torecord from the cortical surface 221 and cortical layers 201 areparticularly useful in the diagnosis of epilepsy. The recorded activityin the patient can be used to determine the electrophysiological originof an epileptic seizure, and can help the physician decide corrective orsurgical action to be taken. In many cases the surgeon may recommend asurgical resection. If performed with this device, the precision of theresection may be improved and lead to better clinical outcomes.Additionally, if the resection is more precise, the patient may be ableto keep additional neurological functionality that could have been lostto a larger resected area.

In some embodiments, selectable microelectrode elements 140 can beactivated to stimulate a neurological target 200. Additionally,functional outcome of the neural stimulation can be used to identify thelocation or position of the microelectrode element 140 by a clinicalevaluation of the patient undergoing the stimulation. For example, amicroelectrode element 140 that is stimulating a cortical layer 201 inthe motor cortex responsible for right hand index finger movement willexperience twitching and or movement in their right hand index finger.As an additional example, a microelectrode element 140 that isstimulating in a cortical layer 201 in the auditory lobe may experiencethe perception of sounds. As an additional example, a microelectrodeelement 140 that is stimulating in a cortical layer 201 in the visualcortex may experience the perception of sight. In this manner, thephysician can determine the positioning of the microelectrode elements140, and the neurological surface probe 101 in the neurological target200.

In some embodiments, the microelectrode elements 140 that are used tostimulate the cortical surface 221 and cortical layers 201 areparticularly useful in the treatment of stroke. The stimulation may notcreate a functional outcome such as movement of limbs, but may improvethe ease with which patients can move. This stimulation applied to themicroelectrode element 140 may be sub-threshold stimulation, meaningthat it will not generate action potentials in neurons, but facilitatethe ability of a neuron to reach the action potential threshold, byaltering the extracellular potential.

In some embodiments, the microelectrode elements 140 that are used tostimulate the cortical surface 221 and cortical layers 201 areparticularly useful in the treatment of chronic pain. The stimulationcan be applied to a region of the sensor cortex where the physician hasconcluded that the region may be linked to the patient's pain. Forexample, a patient that presents himself with chronic pain in the facecan implanted with the device in the general region governing sensationof the face in the sensory cortex. This stimulation can be applied tothe microelectrode element 140 to suppress pathological activity inorder to treat the pain.

Referring now to FIG. 4, a schematic of the cortical neuromodulationdevice 100 is provided. The schematic begins with an external controller170 which the operator can use to functions in the device. The externalcontroller 170 can be in direct electrical contact with the controlcircuitry 160, or wirelessly connected through antenna circuitry. Thecontrol circuitry 160 is used to translate the commands from theexternal controller 170 to stimulate and or record from the device. Thecontrol circuitry 160 is also used to transmit captured information fromthe device to the external controller 170 for display or processing.Subsequently the control circuitry is electrical communication with theneurological surface probe 101. The communication is preferably througha tether wire or ribbon cable (not shown). Protruding from theneurological surface probe 101 are the cortical depth probes 130 athrough 130 n (collectively 130), where n is an arbitrary quantity.Furthermore, each cortical depth probe 130 incorporates at least onemicroelectrode elements 140.

Referring now to FIG. 5A, a top view of the exemplary embodiment in FIG.1 is provided. FIG. 5B is a detailed planar view of the control module150. The image demonstrates the curvature of the upper housing 152, andthe shape of the lower housing 151. In particular, the fixationstructures 156 are designed in order to be slightly offset from theplanar surface of the lower housing 151 in order to be adaptable to allskull shapes, curvatures and sizes.

Referring now to FIG. 6B, an additional perspective view of theneurological surface probe 101 is provided. In the image, cortical depthprobes 130 a through 130 c are the most proximal. In FIG. 6C, aperspective view of the neurological surface probe 101 is demonstratedwhere currents have been applied to a selection of microelectrodes 140.Microelectrodes that have a cathodal signal applied to them are labeled140NEG collectively. Microelectrodes that serve as electrical ground arelabel 140GND collectively. FIG. 6D demonstrates the electric fieldisosurfaces 141 that the applied currents would create. It is understoodby those skilled in the art that any combination of signals (anodal,cathodal, ground) can be applied to any combination of microelectrodes140 in order to create an arbitrary, or intentionally designed,three-dimensional electrical field in the tissue volume where theneurological surface probe 101 has been implanted.

Referring now to FIG. 6B, an additional perspective view of theneurological surface probe 101 is provided. In the image, cortical depthprobes 130 a through 130 c are the most proximal.

Referring now to FIG. 7A, a frontal planar view of the neurologicalsurface probe 101 is provided. In the image cortical depth probes 130 gthrough 130 i are shown. On cortical depth electrode 130 i, themicroelectrode elements 140 are labeled, 140 ia through 140 id. Themicroelectrode element 140 ia is most proximal along the cortical depthprobe 130 i to the planar surface of the neurological surface probe 101.The microelectrode element 140 id is most distal along the corticaldepth probe 130 i to the planar surface of the neurological surfaceprobe 101.

Referring now to FIG. 7B and FIG. 7C, two additional planar views of theneurological surface probe 101 are provided. In the image cortical depthprobes 130 c, 130 f, and 130 i are shown. In FIG. 7B the cortical depthprobe 130 c is the proximal, whereas the cortical depth probe 130 i isthe most distal.

In FIG. 8A, a detailed perspective view of one cortical depth probe 130g is provided. In FIG. 8B an additional detailed perspective view of onecortical depth probe 130 g is provided. The microelectrode elements onthe surface of the cortical depth probe 130 g are labeled 140 ga through140 gd.

FIG. 9 partially demonstrates how the assembly of the neurologicalsurface probe is performed. Additionally, in this example, the corticaldepth probes 130 have not yet been bent down to protrude from thesurface of the neurological surface probe 101. The supportive backinglayer 120 has been constructed as described above. On its surface arecutouts of the structure that will create the cortical depth probe 130which is here referred to as a cortical depth probe backing 132.Likewise, on the microelectrode array film 110, a structure referred toas the cortical depth probe film 135 is implemented. In this exemplaryembodiment, there are nine cortical depth probe backings 132 and ninecortical depth probe films 135.

By a process of bonding, the microelectrode array film 110 is attachedto its supportive backing layer 120. FIG. 10 demonstrates the assembledneurological surface probe 101 after bonding, but before the corticaldepth probes 130 have been bent down to protrude from the planar surfaceof the neurological surface probe 101.

In use, the cortical neuromodulation device 100 is placed surgicallythrough a craniotomy formed in the skull. FIG. 11A is a perspective viewof the placement of the device. The image demonstrates a cross sectionof the brain surface 220 and skull 225. A circular craniotomy 226 hasbeen performed in the skull. The neurological surface probe 101 has beensurgically placed, with its cortical depth probes 130 piercing the duramater (not detailed) and positioned subdurally. The control module 150is placed on a different section of anatomy. It is surgically placed onthe surface of the skull 225 and can be fastened using cranial screws.FIG. 11B demonstrates an additional perspective view of the cut-awayanatomical region. FIG. 11C demonstrates an additional planar side viewof the cut-away anatomical region.

In some embodiments, it is preferable to integrate the control modulewith the neurological surface probe into one device, and avoid a wire orribbon cable tether. The additional embodiment of an integrated corticalneuromodulation device 300 in FIG. 12 demonstrates the integration ofall system components into one module.

FIG. 13 demonstrates an additional perspective view of the alternativeembodiment. In some embodiments, the control circuitry 360 can bedirectly implemented on the microelectrode array film 310. Additionally,in some embodiments, the loop antenna 365 can be implemented on themicroelectrode array film 310.

FIG. 14 demonstrates a planar view of the integrated corticalneuromodulation device 300. The cortical depth probes 330 and theirrespective microelectrode elements 340 protrude from the lower surfaceof the device.

In use, the integrated cortical neuromodulation device 300 is placedsurgically through a craniotomy formed in the skull. FIG. 15 is aperspective view of the placement of the device. The image demonstratesa cross section of the brain surface 321 and skull 325. A circularcraniotomy 326 has been performed in the skull. The integrated corticalneuromodulation device 300 has been surgically placed through thecraniotomy, with its cortical depth probes 330 piercing the dura mater(not detailed) and positioned subdurally. FIG. 16 provides an additionalplanar view of the placement of the device in a cross section of humananatomy.

In some embodiments, it is preferable to have a circular neurologicalsurface probe. FIG. 17A demonstrates a perspective view of a circularneurological surface probe 401. The device incorporates four corticaldepth probes 430. On each cortical depth probe 430 a linear array ofmicroelectrode elements 440 is implemented. Additionally, a largesurface electrode 430, generally of diameter 3 mm, is used to record EEGsignals from the surface of the brain. Finally, a ribbon cable tether480 is used to communicate the microelectrode elements 440 to a controlmodule (not shown) as described in previous embodiments. FIG. 17Bdemonstrates an additional perspective view of the circular neurologicalsurface probe 401. In FIG. 17C, a perspective view of the circularneurological surface probe 401 is demonstrated where currents have beenapplied to a selection of microelectrodes 440. Microelectrodes that havea cathodal signal applied to them are labeled 440NEG collectively.Microelectrodes that serve as electrical ground are label 440GNDcollectively. FIG. 17D demonstrates the electric field isosurfaces 441that the applied currents would create. It is understood by thoseskilled in the art that any combination of signals (anodal, cathodal,ground) can be applied to any combination of microelectrodes 440 inorder to create an arbitrary, or intentionally designed,three-dimensional electrical field in the tissue volume where thecircular neurological surface probe 401 has been implanted.

The circular neurological surface probe 401 is implemented by combininga supportive backing layer with a microelectrode array film. FIG. 18Ademonstrates an exemplary circular supportive backing layer 420. Itconsists of a planar central body from which four cortical depth probebackings 432 protrude. Additionally, at the base of each cortical depthprobe backings 432 are bending slits 433 that facilitate the bending ofthe probe into its final three-dimensional construction. FIG. 18Bdemonstrates the circular microelectrode array film 410 that is used inthe current embodiment. It consists of four cortical depth probe film435 on which the microelectrode elements 440 are disposed. The circularsupportive backing layer 420 and the circular microelectrode array film410 are bonded in a process that attaches them to each other.Subsequently, the cortical depth probes 430 are bent into place.

In some embodiments, it is preferable for a circular neurologicalsurface probe to have a central cortical depth probe. FIG. 18Cdemonstrates an additional embodiment of a circular supportive backinglayer 420C with an additional central cortical depth probe backing432CM. It consists of a planar central body from which four corticaldepth probe backings 432C protrude, and a central cortical depth probebacking 432CM of the same length and dimensions projects from the centerof the circular supportive backing layer 420C. Additionally, at the baseof each cortical depth probe backings 432C are bending slits 433C thatfacilitate the bending of the probe into its final three-dimensionalconstruction. Additionally, at the base of the central cortical depthprobe backing 432CM are bending slits 433CM that facilitate the bendingof the central probe into its final three-dimensional construction.

FIG. 18D demonstrates the circular microelectrode array film 410C thatis used in the current embodiment. It consists of four cortical depthprobe films 435C on which the microelectrode elements 440C are disposed.Additionally, a central cortical depth probe film 434CM of the samelength and dimensions projects from the center of the circularmicroelectrode array film 410C. The circular supportive backing layer420C and the circular microelectrode array film 410C are bonded in aprocess that attaches them to each other. Subsequently, the corticaldepth probes are bent into place, with the central cortical depth probetaking a position that is normal to the plane formed by the planarsection of the supportive backing layer 420C.

Referring now to FIG. 18E, a perspective view of the circularneurological surface probe with central pin 401C is demonstrated. Thecomponents demonstrated in FIG. 18C and FIG. 18D are assembled toimplement this embodiment. It consists of four cortical depth probes430C and a central cortical depth probe 430CM. Microelectrode elements440C are disposed on all five cortical depth probes. The centralcortical depth probe 430CM of the same length and dimensions as thecortical depth probes 430C project from the center of the circularneurological surface probe 401C surface. The circular supportive backinglayer 420C and the circular microelectrode array film 410C are bonded ina process that attaches them to each other. Subsequently, the corticaldepth probes are bent into place, with the central cortical depth probetaking a position that is normal to the plane formed by the planarsection of the supportive backing layer 420C.

Referring now to FIG. 19A a cross-sectional view of a portion of humanbrain anatomy 421 is shown, illustrating the exemplary circularneurological surface probe 401 positioned at a neurological target 422.In general, circular neurological surface probe 401 is representative ofany of the cortical neuromodulation devices described herein. Thecircular neurological surface probe 401 includes an array ofmicroelectrode elements along its individual cortical depth probes.Preferably, circular neurological surface probe 401 is implanted usingby performing craniotomy. Its ribbon cable tether 480 remains outside ofthe human body, while the circular neurological surface probe 401 isimplanted on the surface of the cortex of the brain. As in otherembodiments, individual cortical depth probes are meant to be implantedsubdurally, with the microelectrode elements in contact with at leastone of the subdural layers of the cortex.

Referring now to FIG. 19B, a planar view of the positioning of theexemplary circular neurological surface probe 401 in a portion of humanbrain anatomy 421 referred to as the neurological target 422. Asillustrated, one or more of the microelectrode elements circularneurological surface probe 401 are positioned in intimate contact withthe neurological target 422. One or more additional microelectrodeelements of the circular neurological surface probe 401 may reside atlocations not in the immediate vicinity of the neurological target 422.In at least some embodiments, one or more of the microelectrode elementsare remotely accessible from a proximal end of the circular neurologicalsurface probe 401 via one or more electrically conductive leads (notshown).

In some surgical procedures it would be highly beneficial to the patientto have several circular neurological surface probes 401 implanted inthe region of the neurological target 422K. FIG. 20A demonstrates across-sectional view of a portion of human brain anatomy 421K,illustrating four exemplary circular neurological surface probes 401Kpositioned at a neurological target 422K. FIG. 20B is a more detailedclose-up view of the neurological target 422K. Four circularneurological surface probes 401Ka, 401Kb, 401Kc, 401Kd (collectively401K) were implanted in the neurological target 422K. It is highlybeneficial in some surgical procedures to avoid the sulci 405K on thesurface of the brain. The sulci 405K are regions where the brain surfacefolds and may be highly vascularized. The circular neurological surfaceprobes 401K each have a ribbon cable tether, collectively 480K, that canlead to the external portion of the patient.

In practice the physician will determine how many circular neurologicalsurface probes 401K should be implanted. In some cases, it might bebeneficial to implant only one, as the physician might determine thatthis will provide enough physiological information, or enough of atherapeutic stimulation volume. In some cases, it will be beneficial toimplant a multiplicity of circular neurological surface probes 401 inthe region, in order to increase the probability of finding theneurological target. The decision to implant a certain quantity ofdevices may be taken before the surgery, using surgical planningsoftware. Alternatively, or in addition, the decision can be takenduring the surgery.

In some embodiments, it is preferable to integrate the control modulewith the circular neurological surface probe into one device, and avoida wire or ribbon cable tether. The additional embodiment of anintegrated circular cortical neuromodulation device 401M in FIG. 21Ademonstrates the integration of all system components into one module.The device incorporates four cortical depth probes 430M. On eachcortical depth probe 430M a linear array of microelectrode elements 440Mis implemented. Additionally, a lower housing 451M for control module isimplemented directly above the planar region of the circular supportivebacking layer 420M. The upper housing 452M is intended to encapsulatethe control circuitry 460M and loop antenna 465M which are used tocontrol and transmit information to the integrated circular corticalneuromodulation device 401M. On the surface of the circularmicroelectrode array film 440M are microelectrode array elements 440Mwhich are in communication with the control circuitry 460M throughembedded conductive traces (not shown). FIG. 21B demonstrates anadditional perspective view of the integrated circular neurologicalsurface probe 401M. In this image, the implementation of an EEGelectrode 441M of 3 mm diameter is visible. FIG. 21C is an additionalplanar view of the exemplary integrated circular corticalneuromodulation device 401M.

Referring now to FIG. 22, a perspective view of a human brain anatomy421M is shown with the exemplary embodiment of the integrated circularcortical neuromodulation device 401M implanted in a neurological target422M. In this exemplary embodiment, the connection of a ribbon cabletether the external portion of the patient is not necessary. However, anexternal control module (not shown) is required to communicate with theimplanted device. FIG. 23 demonstrates a more detailed view of theportion of human anatomy 421M and the positioning of the exemplarycircular neurological surface probe 401M in the neurological target422M.

In some surgical procedures, it would be highly beneficial to thepatient to have several integrated circular neurological surface probes401M implanted in the region of the neurological target 422M. FIG. 24 isa close-up perspective view of a portion of human brain anatomy 421M,illustrating five exemplary integrated circular neurological surfaceprobes 401Ma, 401Mb, 401Mc, 401Md, 401Me (collectively 401M) positionedat a neurological target 422M. It is highly beneficial in some surgicalprocedures to avoid the sulci 405M on the surface of the brain. Thesulci 405M are regions where the brain surface folds and may be highlyvascularized. The integrated circular neurological surface probes 401Mcan wirelessly communicate to the external portion of the patient.

In all of the embodiments presented, it is understood that the devicesare meant to be implanted using a surgical procedure on the surface ofthe brain. Additionally, it is intended that the cortical depth probeswhich protrude from all embodiments are meant to be in the subduralregion or the brain, and the microelectrode elements on the surface ofthe cortical depth probes are meant to be in contact with at least oneof the cortical layers. The neurological surface probes are placed onthe brain generally for recording and/or stimulation of the cortex. Theregion of the cortex that the physician is target for diagnosis ortherapy is termed the neurological target.

The microelectrode elements can also be placed in other parts of thebody, such as the retina, the peripheral nervous system for neuralrecording and/or neural stimulation of such portions of an animalanatomy. Although microelectrodes are discussed generally throughout thevarious embodiments, there is no intention to limit the upper or lowersize of the microelectrodes. The devices and methods described hereinare generally scalable, with a microelectrode size determined accordingto the intended application. For at least some of the neurologicalapplications, microelectrodes are dimensioned sub-millimeter. In someembodiments, microelectrodes are dimensioned sub-micron. In someembodiments, the microelectrodes are formed as planar structures havinga diameter of about 50 μm that are arranged in a linear array withcenter to center spacing of about 100 μm. The planar structure of themicroelectrodes can have regular shapes, such as circles, ellipses,polygons, irregular shapes, or a combination of such regular and/orirregular shapes.

FIG. 23A is a schematic diagram of one embodiment of a cortical depthprobe assembly. The microelectrode tip assembly 500 includes asupporting member 502 including an elongated portion terminating in adistal tip 506 and a proximal extension 510. A linear array of threemicroelectrode elements 504 is arranged along a longitudinal axis of theelongated portion of the support member 502. A corresponding number ofthree electrode contacts 508 are located on the proximal extension 510.Each microelectrode element of the array 504 is interconnected to arespective one of the electrode contacts 508 through a respectiveelectrically conducting lead trace 512. In the exemplary embodiment, apolymer layer 514 is applied to at least one surface of the underlyingsupport member 502. Each of the microelectrode leads, electrode contacts508, and interconnecting lead traces 512 is implemented as anelectrically conducting layer on or within the polymer layer 514.Although a linear array of microelectrode elements is shown, otherembodiments are possible with nonlinear, planar, curved surface, andvolumetric (i.e., three-dimensional) distributions of suchmicroelectrodes are possible.

Fabrication Methods

There are several techniques to achieve the microfabricated componentand the required mechanical and electrical characteristics. Thefabrication procedure is a series of procedural steps in which variouslayers are deposited or removed (e.g., etched) to achieve a final form.Exemplary sequence of procedural steps is described herein.

Step 1: The Carrier Wafer and Sacrificial Layer

In a first step illustrated in FIG. 23A, a carrier substrate 650 isprovided, such as a wafer composed of a crystalline material, such asSilicon, or an amorphous material, such as glass, in particular athermal shock resistant borosilicate glass commercially available underthe brand name PYREX®, or other suitable smooth supportive material. Afirst layer 652 comprising at least two sub-layers is applied to asurface of the wafer 650. One of the sub-layers 652 is a sacrificiallayer deposited on the wafer 650, which will be removed in a subsequentelectrochemical etch step. Preferably, the sacrificial sub-layer ispreceded by another sub-layer, referred to as an underlayer, that willserve to form the electrochemical cell required to etch the sacrificiallayer. In the preferred embodiment, the sacrificial sub-layer isAluminum, or an alloy of Aluminum such as AlSi, which has a smallergranularity, whereas the underlayer is a TiW alloy, Chrome, or similarmetal. The sacrificial layer is represented as a black line 652 in theimage below, the carrier wafer 650 is shown in gray. Each of the imagesillustrated in this series represents a cross section of an exemplaryembodiment, and are used herein to describe the procedural steps.

In some embodiments, the sacrificial layer 652, in addition tofacilitating electrochemical removal of the finished device, is toestablish a granularity, or grain size to the surface of the finisheddevice. Namely, the sacrificial layer can add a micro or nano-roughnessto the surface that can be precisely controlled at least in part by theselection of a suitable underlayer. For example, Aluminum can bedeposited by DC Sputtering with a grain size ranging from 5 nm or lessto 600 nm or more. This grain size provides a first grainy surface. Apolymeric layer is subsequently deposited over the grainy sacrificiallayer. This polymeric layer can be locally etched in order to createvias that open onto the grainy sacrificial layer. Subsequently, a metallayer is deposited over the resulting grainy surface, and polymericlayer, in which the deposited metal serves as theneuro-recording/stimulation microelectrode element, and wire trace. Thearea of the metal that falls into the via in the polymeric layer formsthe microelectrode surface. The area of the metal falls on the polymericlayer can be etched into linear traces and form the interconnect betweenmicroelectrodes and bond pads or circuitry. The process is describedbelow as a “backside microelectrode.” Due to such an increase ingranularity over a relatively flat surface, the overall surface area ofthe metal layer will have a higher effective surface area than that areasubtended by the perimeter of the element. Beneficially, the increasedsurface area results in a corresponding decrease in electrical impedanceof the electrode element. This concept is important in that itfacilitates recording, allowing a greater recording fidelity with lesscomplexity due to the reduction in impedance, while maintaining the samesmall diameter that guarantees high localization of the neural activity.An electrically conducting surface of an exemplary microelectrodeelement thus formed is illustrated in the image of FIG. 30.

Step 2: Deposition of First Polymeric Layer

Referring to FIG. 25B, the next step in the fabrication process includesdepositing a first polymeric layer 654—sometimes referred to as a resinlayer 654. The first polymeric layer 654 can be deposited upon thesacrificial layer 652. This can be done by any suitable means known tothose skilled in the art of MEMS processing, by: (i) spin coating aliquid polymer precursor such as Polyimide or Silicone precursor; (ii)depositing a polymer through chemical vapor deposition as is done withparylene-C; or (iii) laminating a polymer sheet 654 onto the wafer 650.In some embodiments, the polymer layer 654 is heated, or baked, topolymerize.

Referring next to FIG. 25C and FIG. 25D, an optional step includesetching of first polymeric layer 654, as may be beneficial whenpreparing a device having one or more backside electrodes, that willultimately be located along an underside of the finished device. In thisoptional step, the first polymeric layer 654 is locally etched in orderto form open areas 652, where metals for such backside microelectrodesmay be later deposited. This step is optional, and unnecessary whenthere is no need for any such backside electrodes on the finisheddevice—all microelectrode contacts being formed on a front surface ofthe finished device. This step is also advantageous, because thebackside electrode metal layer, when included, will also benefit fromthe higher effective surface area that can be gained from thesacrificial layer's granularity.

The etching can be performed by depositing a mask 656 on the firstpolymeric layer 654. Using well established methods for thin filmprocessing, the mask 656 can be photolithographically defined. Forexample, a photosensitive resin 656 is spin coated onto the polymericlayer 654. A process of exposing an unmasked portion of the resin layer657 to UV light is used for those areas in which the operator chooses toremove the polymer layer 654. The device is developed in a solvent thatwill selectively remove only the unmasked areas 657 that were exposed toUV light. This selective etching process locally opens areas of thepolymeric layer 654, by etching, exposing in this instance theunderlayer 652. In some embodiments, the device is etched in oxygenplasma to remove the exposed portion of the polymeric layer 657. Theetch mask 656 may also be removed by the same etching process, but if itis thicker than the polymer layer it may not be completely removed.Illustrated in the figures is a defined etch mask 656. Alternatively orin addition, the etch mask 656 can also be implemented in anon-photodefinable layer, such as Silicon Dioxide deposited by DCSputtering. The Silicon Dioxide then has the photoresist deposited andphotolithographically defined on top of it. After etching the polymericlayer 654, the Silicon Dioxide mask can be optionally removed.

FIG. 25D illustrates the device after the exposed portion of the polymerlayer 657 was removed. As illustrated, a portion of the sacrificiallayer 652 is now exposed. In some embodiments, the photoresist mask 656cab be subsequently removed using a suitable solvent.

Step 3: Deposition and Definition of Metal Layer

The deposition of the layer can also be made through a resist mask 670,as shown in FIG. 25G. In this case a photoresist mask 686′ would bephotolithographically defined on the polymer layer 654. An electricallyconductive (e.g., metal) layer 692′ can then be deposited over themasked device. Thus, unmasked areas 687 at which it is desirable to havean electrically conducting layer 690 formed, are open with respect tothe photoresist mask 686′, such that the a portion of the depositedelectrically conductive layer 692′ lands directly onto the polymericlayer 654 at the unmasked area 687. This technique is sometimes referredto as a “lift off” technique. The photoresist mask 686′, with anyelectrically conductive layer 692′ thereon, is then dissolved, such thatthe only remaining metal 690 is on the polymer at the formerly unmaskedareas. Note that the metal layer 692′ on top of the photoresist 686′ isalso removed by removal of the photoresist mask 686′. Beneficially, thatportion of the electrically conducting layer 690 in contact with thepolymeric layer 654 remains after removal of the mask 686′.

In an alternative method, referring now to FIG. 25H, a metal layer 692″can be deposited onto the entire surface of a wafer 650. As illustrated,the metal layer 692″ is provided on top of the polymeric layer 654,which is provided on top of the sacrificial layer 652. A masking layer686″ is provided over that portion of the metal layer 692″ to remain.Exposed regions of the metal layer 692″ can then be removed locally by aphotolithographic step such as demonstrated below.

Referring next to FIG. 25E, an electrically conductive layer that servesas the electrode 680 and one or more electrically conductive traces 682is next deposited. Such an electrically conductive layer can include ametal layer deposited by any suitable thin-film process, such as DCsputtering, RF Sputtering, or evaporation techniques. The metaldeposited in the electrically conductive layer 680, 682 is preferablyplatinum, iridium, platinum-iridium alloy, iridium-oxide, titanium, or atitanium alloy to ensure acceptable electrical characteristics (such ascharge transfer) and mechanical strength.

In a preferred embodiment, the metal layer 680, 682 is deposited with anadhesion promotion layer in contact with the polymer. For example,titanium can be sputtered onto the polyimide layer 654 in an initialpartial step to improve adhesion, followed by a platinum layer depositedin an intermediate partial step, and optionally, a titanium layer maythem be deposited onto the platinum layer in a subsequent partial step.This creates a Ti—Pt—Ti sandwich, where the titanium is responsible foradhering the platinum to the polyimide on either side of it, and theplatinum is the metal layer that will be used.

For embodiments that produce backside electrodes, as described above inreference to FIG. 25C through FIG. 25E, then the electrically conductivelayer 680 will be in contact with the sacrificial layer 652 in theregion of the backside electrode 680. The metal deposition technique isselected to ensure that there is contact between the metal on top of thepolymeric layer 654, and the metal on the exposed portion of thesacrificial layer 652. This is done by ensuring the metal 680 isconformally deposited, and that the polymeric layer 654 is not toothick. The metal layer 680 can then be photolithographically defined asexplained above. An etch in a plasma, such as Chlorine gas plasma, canbe used to remove the metal layers deposited using a photoresist mask.The photoresist mask can then be removed in a solvent.

Step 4: Deposition of 2nd Polymeric Layer

Referring next to FIG. 25I for a backside electrode embodiment and FIG.25H, a second polymeric layer 672, 692 is deposited using a suitabletechnique, such as any of the techniques described above with respect toFIG. 25B. The second polymeric layer 672, 692 is deposited onto theunderlying polymeric layer 654, 664, and any exposed metal layer 658,668. In some embodiments, the first polymeric layer 654, 664 can beprocessed in order to increase its adhesion to the second polymericlayer 672, 692. For example, such processing can be accomplished throughsurface roughening or chemical alteration using an oxygen plasma. Thesecond insulative, or polymeric layer 672, 692 isolates the electricaltraces, when formed on different layers with respect to each other. Insome embodiments, the polymeric material can be subjected to thermalprocess, such as baking.

Step 5: Definition of Polymeric Layers

Referring next to FIG. 25I through FIG. 25K, to define the one or morepolymer layers 654, 691 and therefore the device itself, an etch mask695 is deposited to an external surface of the device. This etch mask695 may consist of a photodefinable resist but preferably it will be ahard etch mask such as silicon dioxide or amorphous silicon which canwithstand the etch of the polymeric layer without significantdegradation.

The wafer 650 at this point also has a hard mask 693 deposited, forexample, by DC or RF sputtering. A photodefinable 695 resist isdeposited on the hard mask 693 and the areas of the polymer 654, 691that are to be etched are defined.

The hard mask 693 is then etched with a different gas then would be usedto etch the polymeric layer 654, 691, for example CF4 plasma. Now theone or more polymeric layer 654, 691 can be etched with a gas, such asoxygen plasma, to the sacrificial layer 652, as shown. Thus, theremaining portions of the hard mask shown in FIG. 25K define the extentof the device, by defining the device's edges 659.

The remaining portions of the hard mask 693 can be optionally removed ina subsequent step. The goal of this etching process is to: (i) definethe microelectrode sites; (ii) define the device shape; and (iii) definethe contact areas for electronics or wire attachment. A top view of anexemplary finished microelectrode device is shown in FIG. 31. Across-section of another exemplary finished microelectrode device isshown in FIG. 32.

If the option of making backside electrodes is taken in step 2, thedevice will have microelectrodes at its surface once removed from thesubstrate.

Step 6: Optional Bonding of Electronics

If the device is to be integrated with electronics, referring now toFIG. 25L, the contact pads 699 can be used at this point to connect toan electrical circuit device 697. For example, an Integrated Circuitchip 697 can be connected to the contacts 690 (FIG. 25K) by flip-chipbonding the chip 697 to the device 661, using a conductive epoxyinterlayer. The chip 697 can then be further attached by chemicalbonding, such as an epoxy to ensure a strong and reliable connection tothe device 661.

Step 7: Removal of Devices from Carrier Wafer

A final step of the fabrication process is illustrated in FIG. 25M, toremove the device 661, such as a MEMS device, from the underlying wafer650. The sacrificial layer 652 (e.g., FIG. 25L) is electrochemicallyetched away. Removal of the sacrificial layer 652 from under the device661, frees the underside of the device 661 from the wafer 650. This canbe accomplished by placing the wafer in a saline bath with a high NaClconcentration. A platinum electrode in the bath can be used as areference. A voltage is applied to the aluminum layer with respect tothe platinum electrode. The electrochemical cell created by the Aluminumand TiW etches the aluminum, and this etch continues below the devices.The devices fall into the bath and are removed.

FIG. 26 is a micrograph of an embodiment of a backside microelectrodeelement 700. The image is taken at the process step shown in FIG. 25E.The granularity 702 of the aluminum sacrificial layer surface 704 isused to increase the effective surface area of a metal electrode in asubsequent step. Also shown is a portion of an interconnecting lead 706in electrical communication with the microelectrode element 700.

FIG. 27 is a planar view of a construction element of an embodiment of amicroelectrode tip. The construction element includes a stencil frametree 640 including eight rigid backing members 642 releasably attachedto a supporting construction frame 644. Each of the rigid backingmembers 642 includes an elongated portion, and an proximal portionhaving an opening 646 to accommodate one or more electronic devices,when fabricated. The stencil frame tree 640 can be implemented in arigid material, such that each of the individual supporting constructionframes can be bonded to the devices on the carrier wafer.

FIG. 28 is a schematic view of a portion of the construction elementillustrated in FIG. 29, illustrating a close up of the assembledcomponents. In this exemplary embodiment, the polymer devices werefabricated using a “backside” electrodes process

FIG. 29 illustrates an exploded schematic view of a construction elementof an embodiment of a microelectrode array tip. The stencil frame tree400 is placed on a surface of a carrier wafer including micro-arraydevices 649 formed therein. The stencil frame tree 400 is suitablyaligned with the micro-array devices 649 of the carrier wafer 648, andbonded thereto. One or more electronic devices can be suitably placed onthe polymer devices either after or before the stencil frame tree 400 isbonded to the carrier wafer 648.

FIG. 30 is a schematic view of another portion of the constructionelement illustrated in FIG. 29. Once the sacrificial layer has beenremoved as described above, the devices 649 are released from thecarrier wafer 648 and are now bonded to the stencil 640 for support. Inthe exemplary embodiment, the side of the polymeric device 649 facingthe carrier wafer 648 (and in contact with the sacrificial layer) hasthe microelectrodes at its surface. In general, microelectrodes may beincluded in either or both sides as described herein.

In some embodiments, a rigid back 642 on the polymer micro-device 649 isrequired. This renders the device 649 fully, or locally, rigid. Thisrigidity might be advantageous for insertion into tissue. The concept isa stencil shape 640 which can be bonded onto the devices on the carrierwafer where they have been fabricated. The stencil shape 640 can beimplemented in a polymer, such as PEEK or Polyurethane, or in metal suchas Medical Grade Stainless Steel or Titanium. It can be molded intoshape, cut by machining or laser, or stamped out. When this rigidstructure has been attached to the devices, the electronic chip can bebonded. The electronic chip can also be bonded to the devicesbeforehand. After the assembly process the devices can be removed fromthe carrier wafer using the same sacrificial etching techniques asdescribed above. A further assembly procedure can be to remove the rigidbacking from its frame and integrate the device with its finalstructure. In some embodiments, the rigid backing is conductive. Inother embodiments, the rigid backing is non-conductive. When thissupport structure is of a conductive material, it can also serve as theelectrical ground or reference for the stimulation.

FIG. 33A through FIG. 36C are images of additional embodiments, in whichone or more backing layers are used to support a microelectrode film.The one or more backing layers can be rigid, or semi-rigid. In someembodiments, the one or more backing layers can be flexible FIG. 33Aillustrates a planar view of a construction element used to create arectangular array of microelectrode tips. The exemplary constructionelement includes a stencil frame tree 740′ including an arrangement of,in this example, twelve individual semi-rigid backing members 742. Thestencil frame tree 740′ can include a rigid material, such as medicalgrade stainless steel. In some embodiments, the stencil frame tree 740′can be bonded to one or more microelectrode devices, for example, on acarrier wafer.

The stencil frame tree 740′ can be implemented by laser cutting,water-jet cutting, chemical etching using photosensitive masks, oranother method used to obtain medical-grade, two-dimensional structures.The stencil frame tree 740′ can include one or more, open-ended orenclosed, apertures 746, for example, in which microelectronic circuitrycan be located.

The stencil frame tree 740′ is also characterized by its overall shapeand size. Generally, any overall shape is contemplated, includingpolygons, ellipses, circles, serpentines, irregular shapes, and anycombination of such shapes. In the illustrative embodiment, asubstantially rectangular stencil frame tree 740′ is characterized byits width, W, and its length, L. In the exemplary embodiment, the widthis 20 mm, and the length is 15 mm. The stencil frame tree 740′ isgenerally thin to facilitate fabrication and placement within the body.In the exemplary embodiment, the thickness is about 0.1 mm (not shown).Generally, the stencil frame tree 740′ has an overall shape anddimensions conforming to the anatomy for which it is meant to be used.Such target anatomies include any of the anatomies described herein,including the brain, the spine, the peripheral nerve system, thecochlea, the retina, and other parts of the body. In some embodiments,it may have a width as wide as 20 cm or greater, and a length as long as15 cm or greater, although no general limitation as to size and shapeare contemplated.

FIG. 33B is a perspective view of a portion of the stencil frame tree740, illustrating several semi-rigid backing members 742 formed therein.The general shape semi-rigid backing members 742 can be formed by anysuitable means, including pushing, molding, or stamping. Once formed,the semi-rigid backing members 742 can be bent or otherwise formed intoa downwards position as shown in FIG. 33C. In other embodiments, thebacking members 742 can be bent into an upward position, or into acombination of downward and upward positions. This action results inprotruding portions forming a supportive, probe backing member 743. Asmentioned in previous embodiments, this bending can be performed before,or after, a microelectrode film has been attached to the stencil frametree 740′.

FIG. 34A and FIG. 34B demonstrate additional embodiments of a stencilframe tree 740″, 740′″ (generally 740). In some embodiments, the stencilframe tree 740 can include one or more, vertical elongated grooves oropenings 745 a through 745 c (generally 745) in order to make thestencil frame tree 740 more flexible along one or more axes, enabling agenerally planar structure to conform to a portion of anatomy that isnot flat, as shown in FIG. 34A. In some embodiments, the stencil frametree 740 can include one or more, horizontal 746 or vertical elongatedgrooves or openings 745, in order to make it more flexible along severalaxes, enabling it to conform to a portion of anatomy which is not flat,as shown in FIG. 34B.

FIG. 34C and FIG. 34D demonstrate various embodiments of semi-rigidbacking members 742, illustrating different shapes and features. FIG.34C demonstrates a closer view of the embodiment discussed above,characterized by a relatively sharp tip which can promote easierpenetration of tissue, including the dura mater on the surface of thebrain. The rigid members 742, 747 are also characterized by theirrespective length d measured from a base portion to the tip, that can beimplemented to be short, or long enough to reach certain areas ofanatomy. In some embodiments, one or more of the semi-rigid backingmembers 742, 747 of the same stencil frame tree 740 can have differentdimensions and/or different shapes. In some embodiments, e.g., forcranial applications, the length d is generally about 1-4 mm but can beas short as 0.5 mm or less, or as long as several centimeters orgreater.

FIG. 34D illustrates an additional embodiment, characterized by arounded tip which can prevent chronic injury of tissue afterimplantation. The rigid member 747 also differs by an aperture, or gapin its base 748 which can improve the ease of bending the member into isfinal, protruding position. Such a gap 748 can be included in any of theembodiments described herein.

FIG. 35A illustrates a top perspective view of an assembledmicroelectrode assembly 750 that can be used for recording and/orstimulation. In this assembly the rigid stencil frame tree 740′ issupporting a microelectrode film 755 (not shown) on its inferior side.Semi-rigid backing members 742 have been bent downwards to protrude fromits inferior side. A microelectronic circuit element 752 is electricallycoupled between the microelectrode film and an external device (notshown) through flexible electric conduit member 754.

FIG. 35B illustrates in more detail a perspective view of a single rigidbacking member 742 from the inferior side of the assembly 750. Themicroelectrode film 755 is visible, having been bonded to the inferiorside. On the inferior side of the microelectrode film 755 are anarrangement of microelectrode elements 765. The microelectrode film 755and microelectrode elements 765 conform to the bent rigid backing member742, extending away from the plane of the stencil frame tree 740′. Onthe surface of the exemplary embodiment are four microelectrode elementsor sites 765. These sites can also be used for one or more of sensing orrecording neural activity, or electrical stimulation, or they can beenabled to stimulate and record from the same site. The number ofmicroelectrode sites 765 of each bent rigid backing member 742 can varyfrom one or more. In this exemplary embodiment there are fourmicroelectrode stimulation sites 765. They can also be arranged in otherconfigurations, including any of the configurations described herein,such as a tetrode configuration as will be shown in subsequentembodiments, such as in FIG. 42A through FIG. 42D and FIG. 43F throughFIG. 43G.

FIG. 35C illustrates a perspective view of an assembled microelectroderecording and stimulation device 780. In this assembly the rigid stencilframe tree 790 is supporting a microelectrode film 795 on its inferiorside. Semi-rigid backing members 792 have been bent downwards toprotrude from its inferior side. A microelectronic circuit element 782brings the microelectrode film into electrical contact with an externaldevice (not shown) through flexible electric conduit member 784.

FIG. 35D illustrates a closer perspective view of a single rigid backingmember 792 from the inferior side of the assembly 780. Themicroelectrode film 795 has been bonded to the superior side of therigid stencil frame tree 790. The microelectrode film 795 can beimplemented using the micro-fabrication processes described herein, andcan be bonded to the rigid stencil frame tree 790 by gluing or heating.On the superior side of the microelectrode film 795 are microelectrodeelements 796 and 797 which conform to the bent rigid backing member 792.On the surface is a relatively large microelectrode stimulation site 796for stimulating neural activity. Additionally, on the surface is anarrangement of four relatively small microelectrode recording sites 797arranged in a tetrode configuration used for single neural cellrecording. The number of microelectrode stimulation sites 796 on eachrigid backing member 792 can vary from one or more. There are furthertetrode configuration as will be shown in subsequent embodiments, suchas in FIG. 42A through FIG. 42D and FIG. 43F through FIG. 43G.

FIG. 35E illustrates a perspective view of the array of protrudingmicroelectrode elements 762 shown in FIG. 35A. The microelectrode film755 can be implement using any of the microfabrication procedurespreviously described. In this exemplary embodiment, the backsidefabrication process was used. The microelectrode film 755 can be bondedto the stencil tree frame through gluing or heating.

As shown in FIG. 34A and FIG. 34B, it may be necessary to includeelongated gaps in the rigid backing frame 740 and the bondedmicroelectrode film 755 in order for the microelectrode assembly 750 toconform to a portion of anatomy. FIG. 36A shows a portion of humananatomy, the left hemisphere of the brain 771. On its cortical surface,an exemplary microelectrode assembly 750 has been placed, which can beused to record and/or stimulate neural activity.

FIG. 36B illustrates an additional perspective demonstrating both theleft hemisphere 771 and the right hemisphere 772 of the brain. Themicroelectrode assembly 750 has been surgical placed on the cortex, andconnected to a separate control system (not shown) through electricalconduit 754. The separate control system can be located within the body,external to the body, or a combination of internal and external. Thedevice is generally placed by creating a craniotomy. The protrudingrigid members 742 can puncture the dura mater (not shown) therefore notrequiring its surgical removal. Alternatively or in addition, a surgeonwill remove the dura mater, and the protruding members 742 will puncturethe cortex with a depth that is determined by the length of theprotruding member 742.

This is demonstrated in more detail in FIG. 36C, in which an array of 12protruding members 742 have been inserted into the first layers of thecortex. A microelectronic element 752, when included, can be used torecord, stimulate, or both record and stimulate neural activity on eachof the microelectrode sites that have been implemented on each of theprotruding members 742. In some embodiments, one or more of theprotruding members 742 can be actuated independently or in one or moregroupings to record and/or stimulate a desired region addressable by thedevice 250. In general, the microelectrode assembly 750 can beconfigured with any of microelectrode probe described herein, and usedin combination with any of the stimulation and/or recording or sensingdevices described herein.

Electronic Components

The electronic components of the device enable: (i) recording of neuralactivity from the microelectrode array to identify which microelectrodesites are closest to the stimulation region of interest; and (ii)stimulation and modulation of neuronal activity with the microelectrodearray and the ability to select which microelectrode sites stimulating.

The electronics can be implemented using discrete components, integratedcircuit technology, or a combination of both. A black box design of theelectronics is shown below. The electronics can be driven by an existingImplantable Pulse Generator (IPG), but will include a telemetricprogramming interface to properly condition or route the signal from theIPG to the microelectrode array. An embodiment of the electroniccomponents exists which does not require the TPG.

Mechanical Components

The mechanical components and associated assembly processes serve tohouse the device in a hermetic and biocompatible manner. They alsoenable connection to an existing Implantable Pulse Generator or theextra-corporeal control unit. The extra-corporeal unit provides power,programming ability and retrieval of information. It can be implantedmuch like the external cochlear stimulation systems that exist today. Inan embodiment that includes an Implantable Pulse Generator, it wouldserve to retrieve information and program the electrical unit to routethe signals from the IPG to the microelectrode array.

Referring to FIG. 37, a functional block diagram of an exemplaryembodiment of a neurological target stimulator 820 configured in astimulation mode. The stimulator 820 includes an implantable portion 822including a microelectrode array 826 positionable at a neurologicaltarget. The implantable portion 822 also includes a signal generationdevice 828 for actively stimulating the neurological target. In someembodiments, each of the one or more microelectrodes of themicroelectrode array 826 is in communication with a dedicated signalgeneration device 828. The respective stimulation signal provided at anoptimized frequency for each individual microelectrode-tissue interface,based on a peak resistance frequency. The implantable portion 822 caninclude a power source 832, such as a battery. In some embodiments, theimplantable portion 822 also includes a telemetry and control module 834configured for external communication with an extra-corporeal unit 824.Such a feature can be used to provide extra-corporeal control foroperating the implantable portion 822.

Referring to FIG. 37, a functional block diagram of another exemplaryembodiment of a neurological target stimulator 840 is illustratedconfigured in so-called routing mode. The stimulator 840 includes animplantable portion 842 including a microelectrode array 846positionable at a neurological target. The implantable portion 842 alsoincludes a signal routing circuit 850 configured to direct a stimulationsignal to one or more of the microelectrodes 846 for activelystimulating the neurological target. In this embodiment, the stimulationsignal is obtained from a separate, implantable pulse generator 857. Thepulse generator 857 is in communication with the implantable portion 842through an interconnection cable 856 containing one or more signalleads. The implantable portion 842 also includes at least one signalconditioner 848 configured to condition an output signal from the pulsegenerator 857 suitable for stimulation of the neurological targetthrough one or more of the microelectrodes 846. The implantable portion232 generally includes a power source 852, such as a battery. In someembodiments, the implantable portion 842 also includes a telemetry andcontrol module 854 configured to communicate with an extra-corporealunit 844, to provide controls for operating the implantable portion 842.

Filtering of an Existing Signal.

In some embodiments, the signal conditioner 848 include a filteringcircuit to pre-filter or gain adjust (e.g., pre-amplify and/orattenuate) or otherwise condition an existing signal before routing itto a microelectrode array. Several popular filter options includedigital filters, such as infinite impulse response (IIR) filters,electronic filters using one or more electrical components, such asinductors and capacitors, and surface acoustic wave (SAW) devices. Thefilters can be designed through well known filter synthesis techniquesto have a preferred performance features. Some of the controllablefeatures in filter synthesis include filtration bandwidth, cornerfrequency, pass-band ripple, and relative sideband level. Such filtersinclude categories referred to as Butterworth, Chebyshev 1 and 2, andElliptic filters. The particular implementation—whether analog ordigital, passive or active, makes little difference as the output fromany implementation would still match the desired output.

FIG. 39 is a functional block diagram of another embodiment of aneurological microelectrode target stimulator 814 is shown. Thestimulator 814 includes a microelectrode array 815 positionable at aneurological target of interest. The stimulator 814 also includes animpedance analyzer 816 configured for measuring an electrical impedance,a preferred frequency detector 817, and a stimulator 818 forelectrically stimulating the neurological target.

The impedance analyzer 816 can use any of various known techniques formeasuring electrical impedance. Generally, the impedance analyzer 816provides a test electrical signal having known or measurable attributesto the microelectrode-tissue interface. Such attributes include avoltage level of a voltage source, or a current level of a currentsource. The test voltage or current, as the case may be, when applied tothe microelectrode-tissue interface, induces a sensed current or voltageaccording to physical properties of the microelectrode-tissue interface.The impedance analyzer 816 can form a ratio of the test signal to thesensed signal, yielding an impedance value according to Ohm's Law:Z=V/I. As the microelectrode-tissue impedance Z is a complex quantity,each of the test and sensed electrical signals is identified as havingboth a magnitude and a phase.

In operation, the impedance analyzer measures a complex impedance of themicroelectrode-tissue interface surrounding the at least onemicroelectrode 815. The impedance analyzer repeats the measurements atmultiple different frequencies, by varying frequency of the applied testelectrical signal. Preferably, the multiple frequencies span a frequencyrange that includes biologically relevant frequencies. The preferredfrequency detector 817 identifies the measured impedance being closestto a pure resistance. Such a determination can be accomplished byidentifying the measured impedance value having a phase value closest tozero. For example, a measured impedance can be identified having minimumabsolute value phase (i.e., MIN|∠Z|). Such a determination can also beaccomplished by identifying the measured impedance value having aminimum reactance (i.e., MIN(Im{Z})). The frequency at which theimpedance determined to be closest to a pure resistance is identified asa preferred stimulation frequency. The stimulator 818 is then adjustedto provide a stimulation signal at a frequency, or frequency band, at ornear the preferred stimulation frequency. The stimulation signal is thenapplied to the microelectrode array 815.

Illustrated in FIG. 40 is an electronic circuit schematic diagram for anexemplary on board ASIC as shown in the embodiments above. Shown alongthe right hand portion of the schematic diagram are eight stimulationelectrode elements 968 a through 968 h (generally 968) which aregenerally spread between several cortical depth probes. Each one ofthese elements 968 is in electrical communication with a respectiveelectronic device contact 974 a through 974 d and 974 m through 974 p(generally 974). Also illustrated along the right hand portion of theschematic diagram are eight recording electrode elements 969 a through969 h (generally 969). Similarly, the recording contacts are spreadbetween several cortical depth electrodes. Similarly, each of therecording electrode elements 970 is in electrical communication with arespective electronic device contact 974 e through 974 h and 974 jthrough 974 l. For illustrative purposes, the schematic diagram includesa representative electronic device 980. For brevity, the schematicdiagram includes only eight recording and eight stimulation contacts buta full schematic diagram for many more contacts is similar.Additionally, or alternatively, some embodiments will only includerecording electrodes. Additionally, or alternatively, some embodimentswill only include stimulation electrodes. The electronic device mayinclude one or more of a switch or router, a preamplifier, a signalconditioner, a multiplexer, and a controller. The electronic device 980is in electrical communication with all sixteen of the electronic devicecontact elements 974 a through 974 p.

The electronic device 980 is in further communication with wire leadcontacts 976 a through 976 d (generally 976) that are embedded in theexemplary ribbon cable tether. In the illustrative example, the firstwire lead contact 976 a is used for supplying electrical power to themicroelectronic device and/or one or more of the stimulation electrodeelements 968. The second wire lead contact 976 b is used to provide anelectrical ground contact. This ground contact 976 b may include earthground, another electrical ground within the system, such as a chassisground of a medical device connected to the electronic device 980, orsimply a signal return line. A third wire lead contact 976 c correspondsto a control signal that may be used to provide control inputs from anoperator or other medical device, to control configuration and/oroperation of the electronic device 980. Alternatively or in addition,the control signal contact 976 c may be used for control signals fromthe electronic device 980 to another medical device. A fourth wire leadcontact 976 d corresponds to a signal contact as may be used fordirecting electrical activity detected by one or more of the recordingelectrode elements 969 to a recording or display device. Alternativelyor in addition, the signal contact 976 d may be used for directingelectrical stimulation signals from another medical device to one ormore of the stimulation electrode elements 968.

A top view of an exemplary embodiment of a microelectrode assembly 920is illustrated in FIG. 41A. The assembly 920 includes an array ofmicroelectrodes 922 positioned along a distal end of an elongated probesubstrate 924. A first electronic assembly 928 is positioned at aproximal end of the elongated probe substrate 924. The first electronicassembly 928 can include one or more integrated circuit elements 921,such as a microprocessor, and one or more discrete electronic components932. The first electronic assembly 928 is interconnected to each of themicroelectrodes 922 through a respective trace 926 running along theelongated probe substrate 924. The electronic assembly 928 and can beconfigured to implement one or more functions of the implantableneurological stimulator described herein. In some embodiments, theelongated probe substrate also includes at least a portion of theelectronic assembly 928.

In some embodiments, the first electronic circuitry 928 is connected toan implanted pulse generator (not shown) through a cable 924. In someembodiments, as shown, a second electronics assembly (or a portion ofthe first electronics assembly) includes telemetry circuitry 939, suchas a telemetry antenna. In the exemplary embodiment, at least a portionof electronic circuitry 928, 938 is positioned adjacent to themicroelectrodes 922, for example being joined by the elongated probesubstrate 924.

The mechanical components and associated assembly processes serve tohouse the assembly 920 in a hermetic and biocompatible manner. They mayalso enable connection to an existing Implantable Pulse Generator or theextra-corporeal control unit. The extra-corporeal unit can providepower, programming ability, and retrieval of information. In someembodiments, the assembly 920 can be implanted much like currentlyavailable external cochlear stimulation systems. In an embodiment thatincludes an implantable pulse generator, it would serve to retrieveinformation and program the electrical unit to route the signals fromthe implantable pulse generator to the microelectrode array 922.

The device provides highly localized and efficient stimulation byincorporating microfabricated components, electronic components andmechanical components. The microfabricated component consists of amicroelectrode array. This array can be implemented in a polymericmaterial such as polyimide, polyurethane, parylene, or polysiloxane(silicone) and includes thin film or plated layers of a metal or metaloxide with high charge transfer capability such as platinum,platinum-iridium, iridium, iridium oxide or titanium. The polymeric andmetallic layers can be deposited sequentially and formed usingestablished principles of microfabrication such as spin coating, DC/RFsputtering, photolithography, plasma etching, and etching with a maskconsisting of a secondary or sacrificial material such as silicondioxide or photosensitive resist. The metallic layer can be formed tocreate the microelectrode arrays and traces which connect the array tothe electronics and housing. The polymeric layers serve to isolate thetraces from each other but also provide the structure of the implant'sstimulating/recording tip. There are several fabrication methods whichcan be described to build such a microfabricated component.

The electronic or microelectronic components of the device enable: (i)the ability to identify the peak resistance frequency for eachindividual microelectrode site using electrical impedance spectroscopy;(ii) stimulate at the characteristic peak resistance frequency of eachmicroelectrode (this guarantees minimized signal distortion and maximumcharge transfer to the tissue); and (iii) stimulation and modulation ofneuronal activity with the microelectrode array and the ability toselect which microelectrode sites are stimulating.

The electronics can be implemented using discrete components, integratedcircuit technology, digital signal processing (DSP), or a combination ofall three. The electronics can be incorporated in one unit, or can beused in conjunction with an existing implantable pulse generator (IPG).The electronics may include a telemetric programming interface toproperly condition or route the signal from the IPG to themicroelectrode array.

Referring to FIG. 41B, a side view of an exemplary alternativeembodiment of a microelectrode structure is illustrated. In thisembodiment, an electronics assembly 956 is positioned remote from themicroelectrode array 952. The microelectrode array 952 is joined to theelectronics assembly 956 through an arrangement of interconnectingelectrical leads 954. The electronics assembly 956 can be configured toimplement one or more functions of the implantable neurologicalstimulator described herein. As illustrated, the electronics assembly956 can also be connected to an implanted pulse generator (not shown)through an interconnecting cable 960. Alternatively or in addition, theelectronics assembly 956 can include telemetry circuitry forcommunicating with an external telemetry device 962.

The electronics assembly can include an electrical grounding lead forinterconnection to an electrical ground potential 958. In any of theembodiments described herein, impedance measurements and/or stimulationcan be implemented between two or more microelectrodes (e.g., adjacentmicroelectrodes). Alternatively or in addition, impedance measurementsand/or stimulation can be implemented between one or moremicroelectrodes and an electrical ground reference.

Note that a device can be assembled to not include electronics. Thisdevice would then transfer the signal from the Implantable PulseGenerator directly to the electrodes. A device with electronics wouldfirst “pre-filter” the signal before applying to the electronics. This“pre-filter” might take the form of signal filtering in order to achievea certain signal spectrum, multiplexing and routing in order to directsignals from a pulse generator to a choice of microelectrode sites. Thefollowing figures demonstrate the different components and embodiments.

Cortical Depth Probe Embodiments

Various exemplary embodiments of microelectrode array elementconfigurations including tetrode arrangements are illustrated in FIG.42A through FIG. 42D. Referring to FIG. 42A, a microelectrode arrayelement 1000 includes a stimulation electrode 1002 and four recordingelectrodes 1004. In the exemplary embodiment, the stimulation electrode1002 is disc-shaped; however, other shapes are anticipated, such aspolygons, ovals, and irregular shapes. In this embodiment, the recordingelectrodes 1004 are substantially smaller than the stimulation electrode1002, and positioned within the outer perimeter of the stimulationelectrode 1002. In order to accommodate this arrangement, thestimulation electrode includes a respective open area 1006, one for eachof the recording electrodes. In the exemplary embodiment, the recordingelectrodes 1004 are uniformly spaced having about 90° angular separationbetween adjacent pairs.

In general, the open areas 1006 can have any shape, and the shape neednot be the same as the shape of any recording electrode 1004 that may bepositioned therein. In the exemplary embodiments, the open areas 1006 dohave a similar shape, namely a circle, as the disc-shaped recordingelectrodes 1004. The openings are dimensioned larger than the recordingelectrodes 1004, such that the recording electrodes can be placed withinthe open areas 1006, without touching the stimulation electrode 1002. Anannular region of separation exists between the two electrodes 1002,1004. The recording electrodes 1004 may each be similarly shaped and/orsimilarly sized with respect to each other. They may have similar shapeas the stimulation electrode 1002, or have a different shape. In someembodiments, at least some of the recording electrodes 1004 havedifferent shapes and/or different sizes with respect to each other.

In the exemplary embodiment, the four disc electrodes 1004 embeddedwithin the larger, stimulation electrode 1002. The recording electrodes1004 each have a respective diameter of about 50 μm, and a relativeseparation to their nearest neighbors of about 150 μm. The stimulationelectrode has a diameter of 300 μm. In some embodiments, the diameter ofeach recording electrode can range between about 2 μm or less, and about300 μm or more. In some embodiments, the diameter of the stimulationelectrode can range between about 5 μm or less, and about 1,000 μm ormore.

Referring to FIG. 42B, an alternative embodiment of a microelectrodearray element 1010 shows a stimulation electrode 1012 as a non-closeddisc. The outer perimeter of the stimulation electrode 1012 generallyfollows a circular arc, with indentations defining open areas 1016extending in from the perimeter, towards the center of the electrode1012. In particular, four such open areas 1016, or slots, eachaccommodate a respective recording electrode 1014. The recordingelectrode 1014 is positioned toward an inner end of the open area 1016,nearest the center of the stimulation electrode 1012. In at least someembodiments, the recording electrode 1014 is spaced apart from aperimeter of the open area 1016, such that the recording electrode 1014does not touch the stimulation electrode 1012. In some embodiments, theperimeter of the stimulation electrode 1012 are generally rounded,without sharp corners, in order to prevent highly localized fields.Although a four-recording electrode embodiment is shown, otherembodiments are possible including one or more recording electrodespositioned within respective open areas 1016. Although circular shapesare illustrated for each of the stimulation electrode and the recordingelectrode, different shapes can be used. The shapes can be regular, suchas ellipses, polygons, and irregular shapes.

Referring to FIG. 42C, illustrates a similar embodiment of amicroelectrode array element 1020 to that described above, except thattwo tetrodes 1024 a, and 1024 b are embedded within the same stimulationelectrode 1022. The two tetrodes 1024 a, 1024 b can record neuralactivity from different tissue volumes sizes, with differentsensitivities to neural activity. The “inner tetrode” 1024 b can havethe same, or different microelectrode diameters than the “outer tetrode”1024 a. The diagram shows an “inner tetrode” with 50 μm discs, and an“outer tetrode” with 60 μm discs. Other shapes, sizes, and numbers oftetrode elements are possible.

Referring to another microelectrode element embodiment 1030 illustratedin FIG. 42D, a tetrode 1034 is only slightly embedded into thestimulation electrode 1032. As shown, the innermost portion of the openarea 1036 is spaced apart from an outer perimeter of the stimulationelectrode 1032 by a distance less than a diameter of the recordingelement 1034. Such a configuration would allow adjustment andoptimization of the sensitivity and volume of tissue being recorded.

Various embodiments of neurological stimulation devices and techniqueshave been described herein. These embodiments are given by way ofexample and are not intended to limit the scope of the presentdisclosure. It should be appreciated, moreover, that the variousfeatures of the embodiments that have been described may be combined invarious ways to produce numerous additional embodiments.

One or more of any of the microelectrode array elements 1000, 1010,1020, 1030 can be positioned on an elongated planar member, or acortical depth probe, forming a microelectrode array film that is onecomponent of a neurological surface probe. The neurological surfaceprobes described above were composed of at least one cortical depthprobe. In most embodiments the cortical depth probe protrudes from aplanar surface of the neurological surface probe. It is understood thatthe following embodiments, i.e., FIG. 43A through 43J, of cortical depthprobes, can each be used and implemented in the embodiments ofneurological surface probes presented herein.

A series of exemplary cortical depth probes are illustrated in FIG. 43Athrough FIG. 43J. An exemplary cortical depth probe 1040 is illustratedin FIG. 43A. The cortical depth probe 1040 includes four microelectrodeelements 1045. Each of the microelectrode elements 1045 can be used asstimulation or recording electrodes, or combined stimulation-recordingelectrodes. In the present embodiment microelectrode elements 1045 areimplemented with a diameter of 300 um and are spaced by 1 mm. In theillustrative embodiment, the microelectrode elements 1045 are discoidand are spaced apart from each other in a manner to cover a wide lineardepth in the cortical region.

A series of exemplary cortical depth probes are illustrated in FIG. 43Athrough FIG. 43J. An exemplary cortical depth probe 1040 is illustratedin FIG. 43A. The cortical depth probe 1040 includes four microelectrodeelements 1045. Each of the microelectrode elements 1045 can be used asstimulation or recording electrodes, or combined stimulation-recordingelectrodes. In the present embodiment microelectrode elements 1045 areimplemented with a diameter of 300 μm and are spaced by 1 mm. In theillustrative embodiment, the microelectrode elements 1045 are discoidand are spaced apart from each other in a manner to cover a wide lineardepth in the cortical region.

An additional cortical depth probe 1050 is illustrated in FIG. 43B. Thecortical depth probe 1050 includes three microelectrode elements 1055.Each of the microelectrode elements 1055 can be used as stimulation orrecording electrodes, or combined stimulation-recording electrodes. Inthe present embodiment microelectrode elements 1055 are implemented witha diameter of 400 μm and are spaced by 1.5 mm. In the illustrativeembodiment, the microelectrode elements 1055 are discoid and are spacedapart from each other in a manner to cover a wide linear depth in thecortical region.

An additional cortical depth probe 1060 is illustrated in FIG. 43C. Thecortical depth probe 1060 includes two small diameter microelectrodeelements 1065 and two large diameter microelectrode elements 1066. Eachof the microelectrode elements 1065 and 1066 can be used as stimulationor recording electrodes, or combined stimulation-recording electrodes.However, in the present embodiment it may be preferable to use the smalldiameter microelectrode elements 1065 as recording electrodes becausethey are smaller in diameter and may capture more single-unit cellularactivity. Additionally, it may be preferable to use the large diametermicroelectrode elements 1066 as stimulation electrodes because they arelarger in diameter and can transfer more charge to the neural tissueincreasing the efficacy of stimulation. In the present embodiment, smalldiameter microelectrode elements 1065 are implemented with a diameter of300 μm, and large diameter microelectrode elements 1066 are implementedwith a diameter of 700 μm. The microelectrode elements 1065 and 1066 arespaced by 1.2 mm. In the illustrative embodiment, the microelectrodeelements 1065 and 1066 are discoid and are spaced apart from each otherin a manner to cover a wide linear depth in the cortical region.

Another alternative embodiment of a cortical depth probe 1070 isillustrated in FIG. 43D. In this embodiment, each of the cortical depthprobes 1070 include at least one elongated microelectrode elements 1075.Each of the elongated microelectrode elements 1075 can be used asstimulation or recording electrodes, or combined stimulation-recordingelectrodes. In the illustrative embodiment, the elongated microelectrodeelements 1075 are rounded-corner rectangular and are spaced apart fromeach other in a manner to cover a wide linear depth in the corticalregion.

Another alternative embodiment of a cortical depth probe 1080 isillustrated in FIG. 43E. In this embodiment, each of the cortical depthprobes 1080 include at least one elongated microelectrode elements 1085and one discoid microelement 1086. Each of the microelectrode elements1085 and 1086 can be used as stimulation or recording electrodes, orcombined stimulation-recording electrodes. However, in the presentembodiment it may be preferable to use the discoid microelectrodeelements 1085 as recording electrodes because they are smaller indiameter and may capture more single-unit cellular activity.Additionally, it may be preferable to use the elongated microelectrodeelements 1086 as stimulation electrodes because they are larger indiameter and can transfer more charge to the neural tissue increasingthe efficacy of stimulation. In the illustrative embodiment, themicroelectrode elements 1085 and 1086 spaced apart from each other in amanner to cover a wide linear depth in the cortical region.

An exemplary cortical depth probe 1090 is illustrated in FIG. 43F. Thecortical depth probe 1090 includes four microelectrode elements 1095.Each of the microelectrode elements 1095 includes a respectivestimulation electrode 1092 and tetrode arrangement of recordingelectrodes 1094. In the illustrative embodiment, discoid tetrodeelements 1094 are disposed along an external perimeter of a discoidstimulation electrode 1092, such that the tetrode elements 1094 arespaced apart from the outer perimeter of the stimulation electrode 1092.

Another alternative embodiment of a cortical depth probe 1100 isillustrated in FIG. 43G. In this embodiment, each of the cortical depthprobes 1100 include four microelectrode elements 1105. Each of themicroelectrode elements 1105 includes a respective stimulation electrode1102 and tetrode arrangement of recording electrodes 1104. In theillustrative embodiment, discoid tetrode elements 1104 are disposedwithin an open interior region of an annular stimulation electrode 1102,such that the tetrode elements 1104 are spaced apart from the innerannular perimeter of the stimulation electrode 1102.

Another alternative embodiment of a cortical depth probe 1110 isillustrated in FIG. 43H. In this embodiment, each of the cortical depthprobes 1110 include four microelectrode elements 1115. Each of themicroelectrode elements 1115 can be used as stimulation or recordingelectrodes, or combined stimulation-recording electrodes. In theillustrative embodiment, the microelectrode elements 1115 arerectangular and are spaced apart from each other in a manner to cover awide linear depth in the cortical region.

Another alternative embodiment of a cortical depth probe 1120 isillustrated in FIG. 43I. In this embodiment, each of the cortical depthprobes 1120 include at least one microelectrode element group 1125. Inthe present embodiment there are four microelectrode element group 1125.Each of the microelectrode element groups 1125 is composed of at leastone rectangular microelectrode sub-element 1122. In this presentembodiment there are four rectangular microelectrode sub-elements 1122in each of the microelectrode element groups 1125. In some embodimentsthe four rectangular microelectrode sub-elements 1122 are all connectedelectrically, taking advantage of the edge effects to perform moreefficient neurostimulation. In some embodiments the four rectangularmicroelectrode sub-elements 1122 are not connected electrically, and areindependently stimulated. Microelectrode element groups 1125 in additionto collective, or individual, microelectrode sub-elements 1122 can beused as stimulation or recording electrodes, or combinedstimulation-recording electrodes. In the illustrative embodiment, themicroelectrode element groups 1125 are rectangular groups ofmicroelectrode sub-elements 1122 and are spaced apart from each other ina manner to cover a wide linear depth in the cortical region.

Another alternative embodiment of a cortical depth probe 1130 isillustrated in FIG. 43J. In this embodiment, each of the cortical depthprobes 1130 includes at least one graded microelectrode element group1135. Each of the graded microelectrode element groups 1135 is composedof at least one rectangular microelectrode sub-element, collectively1132. In this present embodiment there are five rectangularmicroelectrode sub-elements 1132 in each of the graded microelectrodeelement groups 1135. The rectangular microelectrode sub-elements 1132decrease in width and spacing towards the center of a gradedmicroelectrode element group 1135. For example, in this manner,electrical stimulation performed can focus current to the center of sucha group, while maintaining advantageous and safe electrochemical limits.For example, microelectrode sub-element 1132 a is 300 μm wide,microelectrode sub-element 1132 b is 100 μm wide, and microelectrodesub-element 1132 c is 50 μm wide. In some embodiments the rectangularmicroelectrode sub-elements 1132 are all connected electrically, takingadvantage of the edge effects to perform more efficientneurostimulation. In some embodiments the rectangular microelectrodesub-elements 1132 are not connected electrically, and are independentlystimulated. Graded microelectrode element groups 1135 in addition tocollective, or individual, microelectrode sub-elements 1132 can be usedas stimulation or recording electrodes, or combinedstimulation-recording electrodes. In the illustrative embodiment, thereare two graded microelectrode element groups 1135 of microelectrodesub-elements 1132 but it is understood that more can be implemented.

In practice the operator can connect the neurological surface probe 101to a recorder unit configured to identify certain regions of theneurological target (e.g., the brain) according to the electricalactivity detected by the microelectrode elements shown in FIG. 43Athrough FIG. 43J. In some embodiments, the microelectrode elements usedto record from the neurological target can be the same microelectrodesas those used to stimulate the target in applications in which bothrecording and stimulation are accomplished. Alternatively or inaddition, the microelectrode elements used to record from theneurological target can be separate microelectrode elements from thoseused to stimulate the target. This is demonstrated in embodiments, whereeach cortical depth probe includes one or more recording electrodes andone or more stimulating electrodes. As shown, the dedicated recordingelectrodes are smaller than dedicated stimulation electrodes. In someembodiments, microelectrodes destined for recording may differ in one ormore of size, shape, number, and arrangement from those microelectrodesdestined for stimulation, e.g., using different microelectrodes.

CONCLUSION

Various embodiments of micro-fabricated cortical neuromodulation deviceshave been described herein. These embodiments are giving by way ofexample and are not intended to limit the scope of the presentdisclosure. It should be appreciated, moreover, that the variousfeatures of the embodiments that have been described may be combined invarious ways to produce numerous additional embodiments. Moreover, whilevarious materials, dimensions, shapes, implantation locations, etc. havebeen described for use with disclosed embodiments, others besides thosedisclosed may be utilized without exceeding the scope of the disclosure.

Although some devices described herein are identified as eithercutaneous or chronic, it is understood that such cutaneous devices maybe used in chronically, being implanted for extended periods, or evenindefinitely. Similarly, any devices described herein as being chronic,it is understood that such devices may also be used cutaneously.

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e., “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03

While this disclosure has been particularly shown and described withreferences to various embodiments, it will be understood by thoseskilled in the art that various changes in form and details may be madetherein without departing from the scope of the encompassed by theappended claims.

1-22. (canceled)
 23. An implantable neurological probe comprising: asupportive backing layer; and a flexible substrate disposed on thesupportive backing layer and comprising an insulative layer, aconductive layer comprising one or more conductive traces disposed onthe insulative layer, at least one microelectrode element disposed onthe insulative layer and coupled to the one or more conductive traces,and a second insulative layer disposed on the conductive layer.
 24. Theimplantable neurological probe of claim 23, further comprising at leastone protrusion, the at least one microelectrode element disposedthereon.
 25. The implantable neurological probe of claim 24, wherein alength of the at least one protrusion is not more than about 4 mm. 26.The implantable neurological probe of claim 23, comprising at least onefeature to promote flexibility of the supportive backing layer.
 27. Theimplantable neurological probe of claim 25, wherein the at least onefeature includes an aperture promoting flexibility in a preferreddirection.
 28. The implantable neurological probe of claim 23,comprising a plurality of microelectrode elements, wherein at least oneof the plurality of microelectrode elements is shaped substantiallydifferent from another microelectrode element of the plurality ofmicroelectrode elements.
 29. The implantable neurological probe of claim23, comprising a plurality of microelectrode elements, wherein theplurality of microelectrode elements comprise at least one stimulatingelectrode and at least one detecting electrode.
 30. The implantableneurological probe of claim 29, wherein the at least one stimulatingelectrode is shaped substantially different from the at least onedetecting electrode.
 31. The implantable neurological probe of claim 30,wherein the at least one of the stimulating electrode and the at leastone detecting electrode comprises a plurality of electrically conductingsub-elements.
 32. The implantable neurological probe of claim 31,wherein the at least one of the stimulating electrode and the at leastone detecting electrode comprises a tetrode arrangement of electricallyconducting sub-elements.
 33. The implantable neurological probe of claim23, wherein the at least one microelectrode element is configured as amicro-electromechanical system (MEMS).
 34. The implantable neurologicalprobe of claim 23, further comprising at least one electronic circuitelement in electrical communication with the at least one microelectrodeelement.
 35. The implantable neurological probe of claim 23, wherein theat least one electronic circuit element comprises at least one of aswitch; a router; an amplifier; a controller; a microprocessor; memory;a multiplexer; a filter; an attenuator; a resistor; a capacitor; aninductor; a diode; a transistor; and combinations thereof.
 36. Theimplantable neurological probe of claim 23 wherein the supportivebacking layer is semi-rigid.
 37. The implantable neurological probe ofclaim 23, wherein the supportive backing layer includes medical gradestainless steel.
 38. A method for stimulating a neurological targetcomprising: implanting a neurological probe within a vicinity of aneurological target site, the neurological probe comprising a supportivebacking layer and a flexible substrate disposed on the supportivebacking layer, the flexible substrate comprising an insulative layer, aconductive layer comprising one or more conductive traces disposed onthe insulative layer, at least one microelectrode element disposed onthe insulative layer and coupled to the one or more conductive traces,and a second insulative layer disposed on the conductive layer; andenergizing by a supplied electrical signal, the at least onemicroelectrode element, wherein the at least one microelectrode elementproduces an electric field adapted to stimulate the neurological targetsite.
 39. The method of claim 38, wherein the act of implantingcomprising: positioning a surface of the supportive backing layer alonga surface of a brain.
 40. The method of claim 38, further comprising:recording neurological activity detected by the at least onemicroelectrode element; and repositioning the neurological probe asrequired, until the recorded activity is indicative of the neurologicalprobe being located sufficiently at the neurological target site. 41.The method of claim 38, wherein the supplied electrical signal isobtained from an implanted pulse generator.
 42. An implantableneurological surface probe comprising: a supportive backing layer; aplurality of protrusions, each attached at one end to the supportivebacking layer; a microelectrode film disposed along at least a portionof the supportive backing layer; a plurality of microelectrode elementsdisposed on the microelectrode film and arranged along each of theplurality of protrusions.
 43. The implantable neurological surface probeof claim 42, further comprising an electronic circuit in electricalcommunication with at least some of the plurality of microelectrodeelements.
 44. A method of making an implantable neurological surfaceprobe comprising: shaping a supportive backing layer, the supportivebacking layer comprising at least one protrusion; forming a plurality ofmicroelectrode elements on a microelectrode film; coupling themicroelectrode film along at least a portion of the surface of thesupportive backing layer, such that the plurality of microelectrodeelements are arranged along the plurality of protrusions.
 45. The methodof claim 44, wherein shaping the supportive backing layer comprises oneor more of laser cutting, water-jet cutting, chemical etching using aphotosensitive mask.